The microbes in the gut are crucial for maintaining the body's immune system and overall gut health. However, it is not fully understood how an unstable gut environment can lead to more severe cases of SARS-CoV-2 infection. The gut microbiota also plays a role in the gut-brain axis and interacts with the central nervous system through metabolic and neuroendocrine pathways. The interaction between the microbiota and the host's body involves hormonal, immune, and neural pathways, and any disruption in the balance of gut bacteria can lead to dysbiosis, which contributes to pathogen growth. In this context, we discuss how dysbiosis could contribute to comorbidities that increase susceptibility to SARS-CoV-2. Probiotics and fecal microbiota transplantation have successfully treated infectious and non-infectious inflammatory-related diseases, the most common comorbidities. These treatments could be adjuvant therapies for COVID-19 infection by restoring gut homeostasis and balancing the gut microbiota.
Polyphenolic phytoconstituents have been widely in use worldwide for ages and are categorised as secondary metabolites of plants. The application of polyphenols such as quercetin, resveratrol, curcumin as nutritional supplements has been researched widely. The use of polyphenols and specifically quercetin, for improving memory and mental endurance has shown significant effects among rats. Even though similar results have not been resonated among humans, but preclinical results have encouraged researchers to explore other polyphenols to study the effects as supplements among athletes. The phytopharmacological research has elucidated the use of natural polyphenols to prevent and treat various physiological and metabolic disorders owing to their free radical scavenging properties, anti-inflammatory, anti-cancer, and immunomodulatory effects. In- -spite of the tremendous pharmacological profile, one of the most dominant problem regarding the use of polyphenolic compounds is their low bioavailability. Nanonization is considered as one of the most prominent approaches among many. This article aims to review and discuss the molecular mechanisms of recently developed nanocarrier-based drug delivery systems for polyphenols and their application as drugs and supplements. Nanoformulations of natural polyphenols as bioactive agents, such as quercetin, kaempferol, fisetin, rutin, hesperetin, and naringenin epigalloccatechin- 3-gallate, genistein, ellagic acid, gallic acid, chlorogenic acid, ferulic acid, curcuminoids, and stilbenes is expected to have better efficacy. These delivery systems are expected to provide higher penetrability of polyphenols at cellular levels and exhibit a controlled release of the drugs. It is widely accepted that natural polyphenols do demonstrate significant therapeutic effects. However, the hindrances in their absorption, specificity, and bioavailability can be overcome using nanotechnology.
Ocimum sanctum is a sacred herb of India and is commonly known as 'Tulsi' or 'Holy Basil' in regional languages of the country. Various parts of O. sanctum are recognised to have remarkable therapeutic efficacy, and are therefore used in Indian traditional medicine system, Ayurveda. Scientific studies have shown that O. sanctum has a range of pharmacological activities. The presence of a substantial amount of polyphenols in O. sanctum could be the reason for its excellent bioactivity. Polyphenols are used to prevent or treat oncologic diseases due to their anti-cancer effects, which are related to activation of apoptotic signaling, cell cycle arrest, binding ability with membrane receptors, and potential effects on immunomodulation and epigenetic mechanisms. The poor bioavailability of polyphenols restricts their clinical use. The application of nanonization has been implemented to improve their bioavailability, penetrability, and prolong their anticancer action. The present review analyses the recent preclinical studies related to the chemo-preventive and therapeutic potential of polyphenols present in O. sanctum. Moreover, the current article also examines in-depth the biochemical and molecular mechanisms involved in the antineoplastic actions of the considered polyphenols.