Exuberant inflammation manifesting as a “cytokine storm” has been suggested as a central feature in the pathogenesis of severe coronavirus disease 2019 (COVID-19). This study investigated two prognostic biomarkers, the high mobility group box 1 (HMGB1) and interleukin-6 (IL-6), in patients with severe COVID-19 at the time of admission in the intensive care unit (ICU). Of 60 ICU patients with COVID-19 enrolled and analyzed in this prospective cohort study, 48 patients (80%) were alive at ICU discharge. HMGB1 and IL-6 plasma levels at ICU admission were elevated compared with a healthy control, both in ICU nonsurvivors and ICU survivors. HMGB1 and IL-6 plasma levels were higher in patients with a higher Sequential Organ Failure Assessment (SOFA) score (> 10), and the presence of septic shock or acute kidney injury. HMGB1 and IL-6 plasma levels were also higher in patients with a poor oxygenation status (PaO2/FiO2 < 150 mm Hg) and a longer duration of ventilation (> 7 days). Plasma HMGB1 and IL-6 levels at ICU admission also correlated with other prognostic markers, including the maximum neutrophil/lymphocyte ratio, D-dimer levels, and C-reactive protein levels. Plasma HMGB1 and IL-6 levels at ICU admission predicted ICU mortality with comparable accuracy to the SOFA score and the COVID-GRAM risk score. Higher HMGB1 and IL-6 were not independently associated with ICU mortality after adjustment for age, gender, and comorbidities in multivariate analysis models. In conclusion, plasma HMGB1 and IL6 at ICU admission may serve as prognostic biomarkers in critically ill COVID-19 patients.

The resistance of malaria parasites to the current antimalarial drugs has led to the search for novel effective drugs. Betula alnoides has been traditionally used for the treatment of malaria, but the scientific evidence to substantiate this claim is still lacking. Therefore, the present study aimed at evaluating the antimalarial activity and toxicity of an aqueous stem extract of B. alnoides in a mouse model. The in vivo antimalarial activity of an aqueous stem extract of B. alnoides was determined by a 4-day suppressive test in mice infected with chloroquine-sensitive Plasmodium berghei ANKA. The B. alnoides extract was administered orally at different doses of 200, 400, and 600 mg/kg body weight. The levels of parasitaemia, survival time, body weight change, and food and water consumption of the mice were determined. The acute toxicity of the extract was assessed in the mice for 14 days after the administration of a single oral dose of 5000 mg/kg. An aqueous stem extract of B. alnoides exhibited a significant dose-dependent reduction of parasitaemia in P. berghei-infected mice at all dose levels compared to the reduction in the negative control. Extract doses of 200, 400, and 600 mg/kg body weight suppressed the levels of parasitaemia by 46.90, 58.39, and 71.26%, respectively. The extract also significantly prolonged the survival times of the P. berghei-infected mice compared to the survival times of the negative control mice. In addition, at all dose levels, the extract prevented body weight loss in P. berghei-infected mice. For the acute toxicity, there were no significant alterations in the biochemical parameters and in the histopathology. In conclusion, the aqueous stem extract of B. alnoides possesses antimalarial properties. A single oral dose of 5000 mg/kg body weight had no significant toxic effects on the function and structure of the kidneys and liver. These results support its use in traditional medicine for the treatment of malaria.

Objective. To investigate the antimalarial effects and toxicity of the extracts of the flowers of Tagetes erecta L. and the leaves of Synedrella nodiflora (L.) Gaertn. in a mouse model. Methods. To determine the in vivo antimalarial activity of the extracts, mice were intraperitoneally injected with the Plasmodium berghei ANKA strain and then administered T. erecta or S. nodiflora extract daily for 4 days. Parasitemia was observed by light microscopy. For the detection of acute toxicity, the mice received a single dose of T. erecta or S. nodiflora extract and were observed for 14 days. Biochemical parameters of liver and kidney function and the histopathology of liver and kidney tissues of the acute toxicity group were then examined. Results. T. erecta and S. nodiflora crude extracts at a dose of 600 mg/kg body weight significantly suppressed parasitemia in malaria-infected mice by 65.65% and 62.65%, respectively. Mice treated with 400 mg/kg T. erecta and S. nodiflora crude extracts showed 50.82% and 57.67% suppression, and mice treated with 200 mg/kg displayed 26.33% and 38.57% suppression, respectively. Additionally, no symptoms of acute toxicity were observed in the T. erecta- and S. nodiflora-treated groups. Moreover, no significant alterations in the biochemical parameters of liver and kidney function and no histological changes in the liver or kidney tissues were observed. Conclusions. This study revealed that both T. erecta and S. nodiflora extracts have antimalarial properties in vivo with less toxic effects. Further studies are needed to elucidate the mechanisms of the active compounds from both plants.

Background Novel potent antimalarial agents are urgently needed to overcome the problem of drug-resistant malaria. Herbal treatments are of interest because plants are the source of many pharmaceutical compounds. The Mahanil-Tang-Thong formulation is a Thai herbal formulation in the national list of essential medicines and is used for the treatment of fever. Therefore, this study aimed to evaluate the antimalarial activity of medicinal plants in the Mahanil-Tang-Thong formulation. Methods Nine medicinal plant ingredients of the Mahanil-Tang-Thong formulation were used in this study. Aqueous and ethanolic extracts of all the plants were analyzed for their phytochemical constituents. All the extracts were used to investigate the in vitro antimalarial activity against Plasmodium falciparum K1 (chloroquine-resistant strain) by using the lactate dehydrogenase (pLDH) method and cytotoxicity in Vero cells by using the 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Additionally, an extract with potent in vitro antimalarial activity and no toxicity was selected to determine the in vivo antimalarial activity with Peters’ 4-day suppressive test against the Plasmodium berghei ANKA strain. Acute toxicity was evaluated in mice for 14 days after the administration of a single oral dose of 2000 mg/kg. Results This study revealed that ethanolic extracts of Sapindus rarak DC., Tectona grandis L.f., Myristica fragrans Houtt. and Dracaena loureiri Gagnep. exhibited potent antimalarial activity, with half-maximal inhibitory concentration (IC50) values of 2.46, 3.21, 8.87 and 10.47 μg/ml, respectively, while the ethanolic of the formulation exhibited moderate activity with an IC50 value of 37.63 μg/ml and its aqueous extract had no activity (IC50 = 100.49 μg/ml). According to the in vitro study, the ethanolic wood extract of M. fragrans was selected for further investigation in an in vivo mouse model. M. fragrans extract at doses of 200, 400, and 600 mg/kg body weight produced a dose-dependent reduction in parasitemia by 8.59, 31.00, and 52.58%, respectively. No toxic effects were observed at a single oral dose of 2000 mg/kg body weight. Conclusion This study demonstrates that M. fragrans is a potential candidate for the development of antimalarial agents.

Background Drug resistance exists in almost all antimalarial drugs currently in use, leading to an urgent need to identify new antimalarial drugs. Medicinal plant use is an alternative approach to antimalarial chemotherapy. This study aimed to explore potent medicinal plants from Prabchompoothaweep remedy for antimalarial drug development. Methods Forty-eight crude extracts from Prabchompoothaweep remedy and its 23 plants ingredients were investigated in vitro for antimalarial properties using Plasmodium lactate dehydrogenase (pLDH) enzyme against Plasmodium falciparum K1 strain and toxicity effects were evaluated in Vero cells. The plant with promising antimalarial activity was further investigated using gas chromatography-mass spectrometry (GC-MS) to identify phytochemicals. Antimalarial activity in mice was evaluated using a four-day suppressive test against Plasmodium berghei ANKA at dose of 200, 400, and 600 mg/kg body weight, and acute toxicity was analyzed. Results Of the 48 crude extracts, 13 (27.08%) showed high antimalarial activity against the K1 strain of P. falciparum (IC50 <  10 μg/ml) and 9 extracts (18.75%) were moderately active (IC50 = 11–50 μg/ml). Additionally, the ethanolic extract of Prabchompoothaweep remedy showed moderate antimalarial activity against the K1 strain of P. falciparum (IC50 = 14.13 μg/ml). Based on in vitro antimalarial and toxicity results, antimalarial activity of the aqueous fruit extract of Terminalia arjuna (IC50 = 4.05 μg/ml and CC50 = 219.6 μg/ml) was further studied in mice. GC-MS analysis of T. arjuna extract identified 22 compounds. The most abundant compounds were pyrogallol, gallic acid, shikimic acid, oleamide, 5-hydroxymethylfurfural, 1,1-diethoxy-ethane, quinic acid, and furfural. Analysis of the four-day suppressive test indicated that T. arjuna extract at dose of 200, 400, and 600 mg/kg body weight significantly suppressed the Plasmodium parasites by 28.33, 45.77, and 67.95%, respectively. In the acute toxicity study, T. arjuna extract was non-toxic at 2000 mg/kg body weight. Conclusions The aqueous fruit extract of T. arjuna exerts antimalarial activity against Plasmodium parasites found in humans (P. falciparum K1) and mice (P. berghei ANKA). Acute toxicity studies showed that T. arjuna extract did not show any lethality or adverse effects up to a dose of 2000 mg/kg.