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Effects of artemisinin and hydroxychloroquine on cytokines in experimental sepsis

Büyükcavlak M, Duman I, Eryavuz OD, Ünlü A, Duman A

Trop Biomed, 2022 Dec 01;39(4):547-551.
PMID: 36602214 DOI: 10.47665/tb.39.4.010

Pro-and anti-inflammatory cytokines mediate the inflammatory response in sepsis. Therefore, regulation of cytokines with medications in risky situations may protect the patients from sepsis. Hydroxychloroquine and artemisinin are antimalarial drugs with immunomodulatory properties. In this study, we intended to investigate the effects of artemisinin and hydroxychloroquine on the cytokines released during sepsis in the rat model. Twenty-four rats were randomized into four groups. The control group received oral saline, the sepsis group received oral saline and intraperitoneal lipopolysaccharide toxin (LPS), the artemisinin-treated sepsis group received oral 33.33 mg/kg of artemisinin, and the hydroxychloroquinetreated sepsis group received oral 33.33 mg/kg of hydroxychloroquine before LPS injection. Three hours later, serum cytokines were measured. An increase was detected in TNF-a, IL-1, and IL-6 levels in the sepsis group compared to the control (p<0.01). Oral pretreatment with artemisinin resulted in significant downregulation only of IL-1 levels (p<0.01). Cytokines IL-1 and IL-6 were significantly downregulated in the serum of LPS-induced rats pretreated with oral hydroxychloroquine than rats with sepsis (p<0.01). Decreases observed in TNF-a and IL-10 levels were insignificant. These results demonstrated that both artemisinin and hydroxychloroquine attenuate the release of pro-inflammatory cytokines three hours after LPS-induced sepsis in rats. A significant decrease was observed in serum IL-1 and IL-6 levels with hydroxychloroquine and IL-1 levels with artemisinin. Based on our findings, we suggest that the therapeutic potential of artemisinin and hydroxychloroquine may be beneficial in preventing cytokine storm during sepsis, and further research is needed to determine the optimal timing of administration.

Matched MeSH terms: Hydroxychloroquine/pharmacology
Treatment of preeclampsia with hydroxychloroquine: a review

Abd Rahman R, DeKoninck P, Murthi P, Wallace EM

J Matern Fetal Neonatal Med, 2018 Feb;31(4):525-529.
PMID: 28142291 DOI: 10.1080/14767058.2017.1289511

In this review, we discuss the potential use of antimalarial drugs as an adjuvant therapy for preeclampsia, focusing on the mechanisms of action of this class of drugs in the context of preeclampsia. In particular, hydroxychloroquine has been shown to have various beneficial effects on patients with systemic lupus erythematosus. There are several pathways targeted by the antimalarial drugs that are similar to the pathophysiology of preeclampsia and hence offering opportunities to develop novel therapies to treat the disease. Given the safety profile of hydroxychloroquine in pregnancy, there is merit in exploring the efficacy of this drug as an adjuvant therapy in women with early onset preeclampsia.

Matched MeSH terms: Hydroxychloroquine/pharmacology
Fulltext Pharmacophore modelling of vanillin derivatives, favipiravir, chloroquine, hydroxychloroquine, monolaurin and tetrodotoxin as MPro inhibitors of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)

Law WY, Asaruddin MR, Bhawani SA, Mohamad S

BMC Res Notes, 2020 Nov 11;13(1):527.
PMID: 33176880 DOI: 10.1186/s13104-020-05379-6

OBJECTIVES: The aim of this study was to use Ligand-based pharmacophore modelling approach for four established antiviral drugs, namely remdesivir, lopinavir, ritonavir and hydroxychloroquine for COVID-19 inhibitors as training sets. In this study Twenty vanillin derivatives together with monolaurin and tetrodotoxin were used as test sets to evaluate as potential SARS-CoV-2 inhibitors. The Structure-based pharmacophore modelling approach was also performed using 5RE6, 5REX and 5RFZ in order to analyse the binding site and ligand-protein complex interactions.
RESULTS: The pharmacophore modelling mode of 5RE6 displayed two Hydrogen Bond Acceptors (HBA) and one Hydrophobic (HY) interaction. Besides, the pharmacophore model of 5REX showed two HBA and two HY interactions. Finally, the pharmacophore model of 5RFZ showed three HBA and one HY interaction. Based on ligand-based approach, 20 Schiff-based vanillin derivatives, showed strong MPro inhibition activity. This was due to their good alignment and common features to PDB-5RE6. Similarly, monolaurin and tetrodotoxin displayed some significant activity against SARS-CoV-2. From structure-based approach, vanillin derivatives (1) to (12) displayed some potent MPro inhibition against SARS-CoV-2. Favipiravir, chloroquine and hydroxychloroquine also showed some significant MPro inhibition.

Matched MeSH terms: Hydroxychloroquine/pharmacology
The effects of hydroxychloroquine on endothelial dysfunction

Rahman R, Murthi P, Singh H, Gurusinghe S, Mockler JC, Lim R, et al.

Pregnancy Hypertens, 2016 Oct;6(4):259-262.
PMID: 27939463 DOI: 10.1016/j.preghy.2016.09.001

Hydroxychloroquine is an anti-malarial drug which, due to its anti-inflammatory and immunomodulatory effects, is widely used for the treatment of autoimmune diseases. In a model of systemic lupus erythematosus hydroxychloroquine has been shown to exert protective endothelial effects. In this study, we aimed to investigate whether hydroxychloroquine was endothelial protective in an in vitro model of TNF-α and preeclamptic serum induced dysfunction. We showed that hydroxychloroquine significantly reduced the production of TNF-α and preeclamptic serum induced endothelin-1 (ET-1). Hydroxychloroquine also significantly mitigated TNF-α induced impairment of angiogenesis. These findings support the further assessment of hydroxychloroquine as an adjuvant therapy in preeclampsia.

Matched MeSH terms: Hydroxychloroquine/pharmacology*