Significance: This review discusses the coronavirus disease 2019 (COVID-19) pathophysiology in the context of diabetes and intracellular reactions by COVID-19, including mitochondrial oxidative stress storms, mitochondrial ROS storms, and long COVID.Recent advances: The long COVID is suffered in ~10% of the COVID-19 patients. Even the virus does not exist, the patients suffer the long COVID for even over a year, This disease could be a mitochondria dysregulation disease.Critical issues: Patients who recover from COVID-19 can develop new or persistent symptoms of multi-organ complications lasting weeks or months, called long COVID. The underlying mechanisms involved in the long COVID is still unclear. Once the symptoms of long COVID persist, they cause significant damage, leading to numerous, persistent symptoms.Future directions: A comprehensive map of the stages and pathogenetic mechanisms related to long COVID and effective drugs to treat and prevent it are required, which will aid the development of future long COVID treatments and symptom relief.

The search for new antimalarial drugs has become an urgent requirement due to resistance to the available drugs and the lack of an effective vaccine. In this respect, the present study aimed to evaluate the antimalarial activity of kaempferol against Plasmodium berghei infection in mice as an in vivo model. Chronic toxicity and antimalarial activities of kaempferol alone and in combination with chloroquine were investigated in P. berghei ANKA infected ICR mice using standard procedures. The results showed that chronic administration of 2,000 mg/kg of kaempferol resulted in no overt signs of toxicity as well as no hepatotoxicity, nephrotoxicity, or hematotoxicity. Interestingly, kaempferol exerted significant (P < 0.05) chemosuppressive, chemoprophylactic, and curative activities in a dose-dependent manner. The highest antimalarial activity was found at a dose of 20 mg/kg which resulted in a significantly (P < 0.05) prolonged survival of infected mice. Moreover, combination treatment of chloroquine and kaempferol also presented significant (P < 0.05) antimalarial effects, although the effects were not significantly different from the chloroquine treated group. From the results of the present study, it can be concluded that kaempferol possesses acceptable antimalarial activities. However, further investigation should be undertaken on the mechanism responsible for the observed antimalarial activity.

Malaria is one of the most important infectious diseases in the world. The choice for the treatment is highly limited due to drug resistance. Hence, finding the new compounds to treat malaria is urgently needed. The present study was attempted to evaluate the antimalarial activity of theAnnona muricataaqueous leaf extract inPlasmodium bergheiinfected mice. Aqueous leaf extract ofA. muricatawas prepared and tested for acute toxicity in mice. For efficacy testin vivo, standard 4-day suppressive test was carried out. ICR mice were inoculated with 10⁷parasitized erythrocytes ofP. bergheiANKA by intraperitoneal injection. The extracts (100, 500, and 1000 mg/kg) were then given orally by gavage once a day for 4 consecutive days. Parasitemia, percentage of inhibition, and packed cell volume were subsequently calculated. Chloroquine (10 mg/kg) was given to infected mice as positive control while untreated control was given only distilled water. It was found thatA. muricataaqueous leaf extract at doses of 100, 500, and 1000 mg/kg resulted in dose dependent parasitemia inhibition of 38.03%, 75.25%, and 85.61%, respectively. Survival time was prolonged in infected mice treated with the extract. Moreover, no mortality to mice was observed with this extract up to a dose of 4000 mg/kg. In conclusion, theA. muricataaqueous leaf extract exerted significant antimalarial activity with no toxicity and prolonged survival time. Therefore, this extract might contain potential lead molecule for the development of a new drug for malaria treatment.

Due to the emergence and spread of malaria parasite with resistance to antimalarial drugs, discovery and development of new, safe, and affordable antimalarial are urgently needed. In this respect, medicinal plant extracts are targets to optimize antimalarial actions and restore efficacy of standard antimalarial drugs. The present study was aimed at determining the antimalarial activities ofGynostemma pentaphyllumandMoringa oleiferaleaf extracts in combination with artesunate againstPlasmodium berghei-infected mice.P. bergheiANKA maintained by serial passage in ICR mice were used based on intraperitoneal injection of 1 × 10⁷parasitized erythrocytes and subsequent development of parasitemia. These infected mice were used to investigate the antimalarial activity of artesunate (6 mg/kg) in combination with 500, 1,000, and 2,000 mg/kg ofG. pentaphyllumandM. oleiferaleaf extracts using 4-day suppressive test. It was found that these extracts showed significant (P<0.05) antimalarial activity in dose-dependent manner with percentage of suppression of 45, 50, and 55% forG. pentaphyllumleaf extract and 35, 40, and 50% forM. oleiferaleaf extract. Additionally, artesunate combined with these extracts presented higher antimalarial activity, compared to extract treated alone with percentage of suppression of 78, 91, and 96% forG. pentaphyllumleaf extract and 73, 82, and 91% forM. oleiferaleaf extract. The results indicated that combination treatment ofG. pentaphyllumorM. oleiferaleaf extracts with artesunate was able to increase the antimalarial activity by using low dose of artesunate. Hence, these results justified the combination of these extracts and artesunate in antimalarial herbal remedies.