scholarly journals In vitro efficacy of Artemisia extracts against SARS-CoV-2

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Chuanxiong Nie ◽  
Jakob Trimpert ◽  
Sooyeon Moon ◽  
Rainer Haag ◽  
Kerry Gilmore ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Plant Extracts ◽  
Artemisia Annua ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Herbal Extracts ◽  
Traditional Medicines ◽  
Affect Cell Viability ◽  
Feline Coronavirus

Abstract Background Traditional medicines based on herbal extracts have been proposed as affordable treatments for patients suffering from coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Teas and drinks containing extracts of Artemisia annua and Artemisia afra have been widely used in Africa in efforts to prevent SARS-CoV-2 infection and fight COVID-19. Methods The plant extracts and Covid-Organics drink produced in Madagascar were tested for plaque reduction using both feline coronavirus and SARS-CoV-2 in vitro. Their cytotoxicities were also investigated. Results Several extracts as well as Covid-Organics inhibited SARS-CoV-2 and FCoV infection at concentrations that did not affect cell viability. Conclusions Some plant extracts show inhibitory activity against FCoV and SARS-CoV-2. However, it remains unclear whether peak plasma concentrations in humans can reach levels needed to inhibit viral infection following consumption of teas or Covid-Organics. Clinical studies are required to evaluate the utility of these drinks for COVID-19 prevention or treatment of patients.

scholarly journals In vitro efficacy of Artemisia extracts against SARS-CoV-2

2021 ◽  
Author(s):  
Chuanxiong Nie ◽  
Jakob Trimpert ◽  
Sooyeon Moon ◽  
Rainer Haag ◽  
Kerry Gilmore ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Clinical Studies ◽  
Artemisia Annua ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Herbal Extracts ◽  
Traditional Medicines ◽  
Affect Cell Viability ◽  
Feline Coronavirus

AbstractTraditional medicines based on herbal extracts have been proposed as affordable treatments for patients suffering from coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Teas and drinks containing extracts of Artemisia annua and Artemisia afra have been widely used in Africa in efforts to prevent and fight COVID-19 infections. We sought to study the ability of different A. annua and A. afra extracts and the Covid-Organics drink produced in Madagascar to inhibit SARS-CoV-2 and feline coronavirus (FCoV) replication in vitro. Several extracts as well as Covid-Organics inhibit SARS-CoV-2 and FCoV replication at concentrations that did not affect cell viability. It remains unclear whether peak plasma concentrations in humans can reach levels needed to inhibit viral replication following consumption of teas or Covid-Organics. Clinical studies are required to evaluate the utility of these drinks for COVID-19 prevention or treatment in patients.

scholarly journals Identification of Anti-Severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Oxysterol Derivatives In Vitro

2021 ◽  
Vol 22 (6) ◽  
pp. 3163
Author(s):  
Hirofumi Ohashi ◽  
Feng Wang ◽  
Frank Stappenbeck ◽  
Kana Tsuchimoto ◽  
Chisa Kobayashi ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Viral Replication ◽  
Cultured Cells ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Membrane Vesicles ◽  
Drug Candidates ◽  
Increased Risk ◽  
Derivatives Of

The development of effective antiviral drugs targeting the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is urgently needed to combat the coronavirus disease 2019 (COVID-19). We have previously studied the use of semi-synthetic derivatives of oxysterols, oxidized derivatives of cholesterol as drug candidates for the inhibition of cancer, fibrosis, and bone regeneration. In this study, we screened a panel of naturally occurring and semi-synthetic oxysterols for anti-SARS-CoV-2 activity using a cell culture infection assay. We show that the natural oxysterols, 7-ketocholesterol, 22(R)-hydroxycholesterol, 24(S)-hydroxycholesterol, and 27-hydroxycholesterol, substantially inhibited SARS-CoV-2 propagation in cultured cells. Among semi-synthetic oxysterols, Oxy210 and Oxy232 displayed more robust anti-SARS-CoV-2 activities, reducing viral replication more than 90% at 10 μM and 99% at 15 μM, respectively. When orally administered in mice, peak plasma concentrations of Oxy210 fell into a therapeutically relevant range (19 μM), based on the dose-dependent curve for antiviral activity in our cell-based assay. Mechanistic studies suggest that Oxy210 reduced replication of SARS-CoV-2 by disrupting the formation of double-membrane vesicles (DMVs); intracellular membrane compartments associated with viral replication. Our study warrants further evaluation of Oxy210 and Oxy232 as a safe and reliable oral medication, which could help protect vulnerable populations with increased risk of developing COVID-19.

scholarly journals In vitro efficacy of Artemisinin-based treatments against SARS-CoV-2

2020 ◽  
Author(s):  
Kerry Gilmore ◽  
Yuyong Zhou ◽  
Santseharay Ramirez ◽  
Long V. Pham ◽  
Ulrik Fahnøe ◽  
...  
Keyword(s):  
Artemisia Annua ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Active Pharmaceutical Ingredients ◽  
Proof Of Concept ◽  
Plaque Reduction Assay ◽  
Prophylactic Efficacy ◽  
Pharmaceutical Ingredients ◽  
Reduction Assay

AbstractEffective and affordable treatments for patients suffering from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are needed. We report in vitro efficacy of Artemisia annua extracts as well as artemisinin, artesunate, and artemether against SARS-CoV-2. The latter two are approved active pharmaceutical ingredients of anti-malarial drugs.Proof-of-concept for prophylactic efficacy of the extracts was obtained using a plaque-reduction assay in VeroE6 cells. Subsequent concentration-response studies using a high-throughput antiviral assay, based on immunostaining of SARS-CoV-2 spike glycoprotein, revealed that pretreatment and treatment with extracts, artemisinin, and artesunate inhibited SARS-CoV-2 infection of VeroE6 cells. In treatment assays, artesunate (50% effective concentration (EC50): 7 μg/mL) was more potent than the tested plant extracts (128-260 μg/mL) or artemisinin (151 μg/mL) and artemether (>179 μg/mL), while generally EC50 in pretreatment assays were slightly higher. The selectivity index (SI), calculated based on treatment and cell viability assays, was highest for artemisinin (54), and roughly equal for the extracts (5-10), artesunate (6) and artemether (<7). Similar results were obtained in human hepatoma Huh7.5 cells. Peak plasma concentrations of artesunate exceeding EC50 values can be achieved. Clinical studies are required to further evaluate the utility of these compounds as COVID-19 treatment.

scholarly journals In vitro efficacy of artemisinin-based treatments against SARS-CoV-2

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuyong Zhou ◽  
Kerry Gilmore ◽  
Santseharay Ramirez ◽  
Eva Settels ◽  
Karen A. Gammeltoft ◽  
...  
Keyword(s):  
Artemisia Annua ◽  
Peak Plasma ◽  
Antiviral Treatment ◽  
Plasma Concentrations ◽  
Cell Types ◽  
Human Lung Cancer ◽  
Therapeutic Window ◽  
Entry Level ◽  
Post Entry

AbstractEffective and affordable treatments for patients suffering from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are needed. We report in vitro efficacy of Artemisia annua extracts as well as artemisinin, artesunate, and artemether against SARS-CoV-2. The latter two are approved active pharmaceutical ingredients of anti-malarial drugs. Concentration–response antiviral treatment assays, based on immunostaining of SARS-CoV-2 spike glycoprotein, revealed that treatment with all studied extracts and compounds inhibited SARS-CoV-2 infection of VeroE6 cells, human hepatoma Huh7.5 cells and human lung cancer A549-hACE2 cells, without obvious influence of the cell type on antiviral efficacy. In treatment assays, artesunate proved most potent (range of 50% effective concentrations (EC50) in different cell types: 7–12 µg/mL), followed by artemether (53–98 µg/mL), A. annua extracts (83–260 µg/mL) and artemisinin (151 to at least 208 µg/mL). The selectivity indices (SI), calculated based on treatment and cell viability assays, were mostly below 10 (range 2 to 54), suggesting a small therapeutic window. Time-of-addition experiments in A549-hACE2 cells revealed that artesunate targeted SARS-CoV-2 at the post-entry level. Peak plasma concentrations of artesunate exceeding EC50 values can be achieved. Clinical studies are required to further evaluate the utility of these compounds as COVID-19 treatment.

scholarly journals Evaluation and Comparison of Antibacterial Efficacy of Herbal Extracts in Combination with Antibiotics on Periodontal pathobionts: An in vitro Microbiological Study

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 89 ◽  
Author(s):  
Shahabe Abullais Saquib ◽  
Nabeeh Abdullah AlQahtani ◽  
Irfan Ahmad ◽  
Mohammed Abdul Kader ◽  
Sami Saeed Al Shahrani ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Plant Extracts ◽  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Synergistic Activity ◽  
Antibacterial Efficacy ◽  
Herbal Extracts ◽  
Inhibition Zones

Background: In the past few decades focus of research has been toward herbal medicines because of growing bacterial resistance and side effects of antimicrobial agents. The extract derived from the plants may increase the efficacy of antibiotics when used in combination against pathogenic bacteria. In the current study, the synergistic antibacterial efficacy of plant extracts in combination with antibiotics has been assessed on selected periodontal pathogens. Methods: Ethanolic extracts were prepared from Salvadora persica (Miswak) and Cinnamomum zeylanicum (Ceylon cinnamon), by the soxhalate method. Plaque samples were collected from clinical periodontitis patients to isolate and grow the periodontal pathobionts under favorable conditions. Susceptibility of bacteria to the extracts was assessed by gauging the diameter of the inhibition zones. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of plant extracts were determined against each bacterium. Synergistic activity of plants extract in combination with antibiotics against the bacteria was also assessed by measuring the diameter of the inhibition zones. Results: Ethanolic extract of both the plants showed an inhibitory effect on the proliferation and growth of all four strains of periodontal pathobionts. Maximum antibacterial activity was exhibited by C. zeylanicum against Tannerella forsythia (MIC = 1.56 ± 0.24 mg/mL, MBC = 6.25 ± 0.68 mg/mL), whereas among all the studied groups the minimum activity was reported by C. zeylanicum against Aggregatibacter actinomycetemcomitans the (MIC = 12.5 ± 3.25 mg/mL, MBC = 75 ± 8.23 mg/mL). Combination of herbal extracts with different antibiotics revealed a synergistic antibacterial effect. The best synergism was exhibited by S. persica with metronidazole against A. actinomycetemcomitans (27 ± 1.78). Conclusions: Current in vitro study showed variable antibacterial activity by experimented herbal extracts against periodontal pathobionts. The synergistic test showed significant antibacterial activity when plant extracts were combined with antibiotics.

scholarly journals Vancomycin In Vitro Bactericidal Activity and Its Relationship to Efficacy in Clearance of Methicillin-Resistant Staphylococcus aureus Bacteremia

2007 ◽  
Vol 51 (7) ◽  
pp. 2582-2586 ◽  
Author(s):  
Pamela A. Moise ◽  
George Sakoulas ◽  
Alan Forrest ◽  
Jerome J. Schentag
Keyword(s):  
Staphylococcus Aureus ◽  
Median Time ◽  
Bactericidal Activity ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Accessory Gene ◽  
Vancomycin Therapy ◽  
Methicillin Resistant ◽  
Vancomycin Mics

ABSTRACT We examined the relationship between the time to clearance of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia while patients were receiving vancomycin therapy and the in vitro bactericidal activity of vancomycin. Vancomycin killing assays were performed with 34 MRSA bloodstream isolates (17 accessory gene regulator group II [agr-II] and 17 non-agr-II isolates) from 34 different patients with MRSA bacteremia for whom clinical and microbiological outcomes data were available. Vancomycin doses were prospectively adjusted to achieve peak plasma concentrations of 28 to 32 μg/ml and trough concentrations of 8 to 12 μg/ml. Bactericidal assays were performed over 24 h with ∼107 to 108 CFU/ml in broth containing 16 μg/ml vancomycin. The median time to clearance of bacteremia was 6.5 days for patients with MRSA isolates demonstrating ≥2.5 reductions in log10 CFU/ml at 24 h and >10.5 days for patients with MRSA isolates demonstrating <2.5 log10 CFU/ml by 24 h (P = 0.025). The median time to clearance was significantly longer with MRSA isolates with vancomycin MICs of 2.0 μg/ml compared to that with MRSA isolates with MICs of ≤1.0 μg/ml (P = 0.019). The bacteremia caused by MRSA isolates with absent or severely reduced delta-hemolysin expression was of a longer duration of bacteremia (10 days and 6.5 days, respectively; P = 0.27) and had a decreased probability of eradication (44% and 78%, respectively; P = 0.086). We conclude that strain-specific microbiological features of MRSA, such as increased vancomycin MICs and decreased killing by vancomycin, appear to be predictive of prolonged MRSA bacteremia while patients are receiving vancomycin therapy. Prolonged bacteremia and decreased delta-hemolysin expression may also be related. Evaluation of these properties may be useful in the consideration of antimicrobial therapies that can be used as alternatives to vancomycin for the treatment of MRSA bacteremia.

scholarly journals Cytotoxic Activity of Camptothecin and Paclitaxel in Newly Established Continuous Human Medullary Thyroid Carcinoma Cell Lines

2004 ◽  
Vol 89 (5) ◽  
pp. 2397-2401 ◽  
Author(s):  
K. Kaczirek ◽  
M. Schindl ◽  
A. Weinhäusel ◽  
C. Scheuba ◽  
C. Passler ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Cell Lines ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Medullary Thyroid ◽  
Cell Counts ◽  
In Vitro Investigation ◽  
Ic50 Values

At the time of diagnosis, more than one quarter of patients with medullary thyroid carcinoma (MTC) has distant metastases. Only few of these patients can be cured by surgery. Standard chemotherapy is characterized by low response rates and short response time. The establishment of eight human MTC cell lines provides a new basis for in vitro investigation of cytotoxic drugs. Camptothecin (CPT) and paclitaxel, which never have been investigated in the treatment of MTC, were tested for their cytotoxic profile in comparison with the clinically ineffective dacarbazine. Eight MTC cell lines were established from seven patients with MTC. IC50 values were calculated from dose-response relationships using cell counts and a formazan dye assay (WST-1). IC50 values were 3.5 ± 1.2 nmol/liter for CPT and 8.2 ± 1.9 nmol/liter for paclitaxel. Dacarbazine showed no reduction of cell proliferation at concentrations 10-fold higher than clinically achievable. Given peak plasma concentrations of 65 ± 20 nmol/liter for CPT and 1 μmol/liter for paclitaxel, these promising in vitro results provide a basis for the performance of clinical trials in patients with advanced MTC.

Inhibitory Effect of Piracetam on Platelet-rich Thrombus Formation in an Animal Model

1998 ◽  
Vol 79 (01) ◽  
pp. 222-227 ◽  
Author(s):  
F. Stockmans ◽  
W. Deberdt ◽  
Å. Nyström ◽  
E. Nyström ◽  
J. M. Stassen ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Ex Vivo ◽  
Peak Plasma ◽  
Thrombus Formation ◽  
Plasma Concentrations ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Cell Deformability

SummaryIntravenous administration of piracetam to hamsters reduced the formation of a platelet-rich venous thrombus induced by a standardised crush injury, in a dose-dependent fashion with an IC50 of 68 ± 8 mg/kg. 200 mg/kg piracetam also significantly reduced in vivo thrombus formation in rats. However, in vitro aggregation of rat platelets was only inhibited with piracetam-concentrations at least 10-fold higher than plasma concentrations (6.2 ± 1.1 mM) obtained in the treated animals. No effects were seen on clotting tests.In vitro human platelet aggregation, induced by a variety of agonists, was inhibited by piracetam, with IC50’s of 25-60 mM. The broad inhibition spectrum could be explained by the capacity of piracetam to prevent fibrinogen binding to activated human platelets. Ex vivo aggregations and bleeding times were only minimally affected after administration of 400 mg/kg piracetam i.v. to healthy male volunteers, resulting in peak plasma levels of 5.8 ± 0.3 mM.A possible antiplatelet effect of piracetam could be due to the documented beneficial effect on red blood cell deformability leading to a putative reduction of ADP release by damaged erythrocytes. However similarly high concentrations were needed to prevent stirring-induced “spontaneous” platelet aggregation in human whole blood.It is concluded that the observed antithrombotic action of piracetam cannot satisfactorily be explained by an isolated direct effect on platelets. An additional influence of piracetam on the rheology of the circulating blood and/or on the vessel wall itself must therefore be taken into consideration.

Performance of Murine Soluble Thrombomodulin (rmsTM) in a Murine Model of Endotoxin-Induced Sepsis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3933-3933
Author(s):  
David E. Joyce ◽  
Haifeng Xu ◽  
Sumeet Mathur ◽  
Francis J. Castellino
Keyword(s):  
Protein C ◽  
Time Course ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Initial Time ◽  
Survival Study ◽  
Sepsis Model ◽  
Survival Difference

Abstract The endothelial surface protein thrombomodulin (TM) generates activated protein C (aPC) that protects from sepsis-related DIC, vascular inflammation, and apoptosis. The purpose of this study is to evaluate a novel recombinant mouse soluble TM (Eli Lilly, Indianapolis, IN) in a murine lethal endotoxin (LPS) sepsis model to determine both kinetic and survival endpoints. A dose effective in rodent reperfusion studies was employed in this sepsis model (D. Berg, Eli Lilly). C57BL6 mice were injected concomitantly with rmsTM 5 mg/kg (s.c.) and LPS 14 ug/g (i.p.) at time zero. Plasma concentrations were determined from citrated plasma at 3, 12, 24, and 48 hr, and plasma rmsTM concentrations were determined by ELISA. In vitro determinations of mouse aPC amidolytic activity and rmsTM dependent fibrinogen clotting time assays utilized rmsTM, murine thrombin, fibrinogen, and Protein C (Enzyme Research Labs). The in-vivo time-dependent mouse plasma kinetic studies confirmed plasma concentrations comparable to that achieved in human sTM antithrombotic studies. Thus, an rmsTM dose of 5 mg/kg was chosen for the 7-day LPS survival study (20% survival model). Twenty age-and weight-matched male C57BL6 mice, age 8–14 weeks, were treated with LPS 14 ug/g or LPS and rmsTM, 5 mg/kg, s.c. Survival curves were analyzed by Wilcoxon rank sum test (power 80%, alpha 2.5, p&lt;0.05). An initial time course after rmsTM s.c. injection yielded a peak plasma rmsTM level at 3 hr (5,000 ng/mL) which persisted up to 48 hr (2,000 ng/mL). In vitro activation of aPC was saturating (2,000 ng/mL aPC with &lt;20 ng/mL rmsTM). Prolongation of the thrombin clot time occurred at approximately 10 ug/ml of rmsTM. The LPS survival study in C57BL6 administered LPS (14 ug/g, i.p.) or LPS and rmsTM 5mg/kg s.c. demonstrated no survival difference (P=0.63). In vitro evaluation of aPC generation by rmsTM yielded ample amounts of aPC. Similarly, reduction of thrombin activity by rmsTM occurred at higher rmsTM concentrations. Thus, the lack of survival difference seen between endotoxemic mice treated with saline or adjunctive rmsTM in this model may be from the lack of thrombin inhibition, the lack of persistent (rmsTM:Thrombin) PC activation, or by more efficient clearance of aPC. Species specificity of TM is less likely a contributing factor. Further elucidation of the murine thrombin/thrombomodulin regulatory mechanism in vivo may be necessary to help explain our unexpected sTM survival results.

scholarly journals Pharmacokinetic and Pharmacodynamic Evaluation of Marbofloxacin in Pig against Korean Local Isolates ofActinobacillus pleuropneumoniae

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Md. Akil Hossain ◽  
Hae-chul Park ◽  
Kyunghun Jeong ◽  
Yang ho Jang ◽  
Dae Gyun Kim ◽  
...  
Keyword(s):  
Body Weight ◽  
Ex Vivo ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Antibacterial Activities ◽  
Time Intervals ◽  
Concentration Time ◽  
Elimination Half ◽  
The Mean

The pharmacokinetics of marbofloxacin in pigs after intravenous (i.v.), intramuscular (i.m.), and peroral (p.o.) administration and pharmacokinetic/pharmacodynamic indices of this drug against Korean local isolates ofActinobacillus pleuropneumoniaewere determined in this study. Marbofloxacin (2.50 mg/kg of body weight) was administered, and blood samples were collected with designated time intervals. Plasma-extracted marbofloxacin was injected into the LC-MS/MS system. The in vitro and ex vivo antibacterial activities of marbofloxacin were evaluated against 20 isolates ofA. pleuropneumoniae. The mean peak plasma concentrations (Cmax) after i.v., i.m., and p.o administration were2.60±0.10,2.59±0.12, and2.34±0.12 µg/mL at0.25±0.00,0.44±0.10, and1.58±0.40 h, respectively. The area under the plasma concentration-time curves (AUC0–24) and elimination half-lives were24.80±0.90,25.80±1.40, and23.40±5.00 h·μg/mL and8.60±0.30,12.80±1.10, and8.60±0.00 h, for i.v., i.m., and p.o. administration, correspondingly. The AUC0–24/MICs of marbofloxacin after i.v., i.m., and p.o. administration were253.86±179.91,264.1±187.16, and239.53±169.75 h, respectively. TheCmax/MIC values were26.58±18.84,26.48±18.77, and23.94±16.97, and T>MICs were42.80±1.01,36.40±1.24, and38.60±1.18 h, after i.v., i.m., and p.o. administration, respectively. Thus, marbofloxacin dosage of 2.50 mg/kg of body weight by i.v., i.m., and p.o. administration with 24 h dosing interval will provide effective treatment for the infection of pig byA. pleuropneumonia.

Sign in / Sign up

Export Citation Format

Share Document