Emergence of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection, COVID‐19, has become the global panic since December 2019, which urges the global healthcare professionals to identify novel therapeutics to counteract this pandemic. So far, there is no approved treatment available to control this public health issue; however, a few antiviral agents and repurposed drugs support the patients under medical supervision by compromising their adverse effects, especially in emergency conditions. Only a few vaccines have been approved to date. In this context, several plant natural products‐based research studies are evidenced to play a crucial role in immunomodulation that can prevent the chances of infection as well as combat the cytokine release storm (CRS) generated during COVID‐19 infection. In this present review, we have focused on flavonoids, especially epicatechin, epigallocatechin gallate, hesperidin, naringenin, quercetin, rutin, luteolin, baicalin, diosmin, ge nistein, biochanin A, and silymarin, which can counteract the virus‐mediated elevated levels of inflammatory cytokines leading to multiple organ failure. In addition, a comprehensive discussion on available in silico, in vitro, and in vivo findings with critical analysis has also been evaluated, which might pave the way for further development of phytotherapeutics to identify the potential lead candidatetoward effective and safe management of the SARS‐CoV‐2 disease.

Rottlerin is a key bioactive phytoconstituent present in the pericarp of Mallotus philippensis. It shows promising multifaceted pharmacological actions against cancer. However, there is hardly any report for the quantification of rottlerin in the biological matrix and on its pharmacokinetic behavior. Therefore, we aimed in the present study to assess selective in vitro ADME properties and in vivo pharmacokinetics of isolated and characterized rottlerin using a newly developed and validated liquid chromatography−tandem mass spectrometry-based highly sensitive bioanalytical method. The method was found to be simple (mobile phase and analytical column), sensitive (1.9 ng/ mL), and rapid (run time of 2.5 min). All the validation parameters were within the acceptable criteria of the United States Food and Drug Administration's bioanalytical method validation guideline. The method was found to be very useful to assess lipophilicity, plasma stability, metabolic stability, plasma protein binding of rottlerin, as well as its oral and intravenous pharmacokinetics in mice. Rottlerin showed a number of drug-like pharmacokinetic properties (in vitro). Moreover, it displayed an excellent half-life (>2 h) and oral bioavailability (>35%) as compared to other members of natural phenolics. The present study is the first-time report of in vitro ADME properties and in vivo preclinical pharmacokinetics of rottlerin. The generated information is very much useful for its further development as a phytotherapeutics toward cancer therapy.

Safranal, a plant secondary metabolite isolated from saffron, has been reported for several promising pharmacological properties toward the management of Alzheimer's disease. In the present study, we observe and report for the first time about several druglike attributes of safranal, such as adherence to Lipinski's rule of five; optimum lipophilicity; high permeability; low blood-to-plasma ratio; less to moderate propensity to interact with P-glycoprotein (P-gp) or breast cancer-resistant protein (BCRP) transporters; and high plasma protein binding as common to most of the marketed drugs using in vitro and ex vivo models. In spite of the above attributes, in vivo oral absorption was found to be very poor, which is linked to the structural integrity of safranal in simulated gastric fluid, simulated intestinal fluid, plasma, and liver microsomes. Moreover, the presence of unsaturated aldehyde moiety in safranal remains in equilibrium with its hydroxylated acetal form. Further research work is required to find out the stable oral absorbable form of safranal by derivatization of its aldehyde group without losing its potency.