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Chemopreventive approaches with food‐derived phytochemicals are progressively rising as a significant aspect of tumor management and control. Herein, we have showcased the major phytoconstituents belonging to the group of flavanoid, as anti‐cancer agents used for the treatment and prevention of hepatocellular carcinoma (HCC). Sorafenib is the sole drug used for the treatment of advanced HCC, but its clinical application is limited because of its severe adverse effects and drug resistance. Diet‐based chemoprevention seems to be the way forward for this disease of malignant nature. As HCC is derived from a chronic inflammatory milieu, the regular incorporation of bioactive phytochemicals in the diet will confer protection and prevent progression to hepatocarcinogenesis. Many preclinical studies proved that the health benefits of flavonoids confer cytotoxic potential against various types of cancers including hepatocellular carcinoma. As flavonoids with excellent safety profile are abundantly present in common vegetables and fruits, they can be better utilized for chemoprevention and chemosensitization in such chronic condition. This review highlights the plausible role of the eight most promising flavonoids (Curcumin, Kaempferol, Resveratrol, Quercetin, Silibinin, Baicalein, Galangin and Luteolin) as key orchestrators of chemoprevention in hepatocellular carcinoma with preclinical and clinical evidence. An attempt to address the challenges in its clinical translation is also included. This review also provides an insight into the close association of HCC and metabolic disorders which may further decipher the chemopreventive effect of dietary bioactive from a proof of concept to extensive clinical translation. Practical applications According to GLOBOCAN 2020 database, it is estimated that 905,677 new cases of liver cancer and approximately 830,180 deaths related to that. The cancer incidence and mortality are almost similar as it is diagnosed at an advanced stage in patients where systemic drug therapy is the sole approach. Due to the emergence of multidrug resistance and drug‐related toxicities, most of the patient can not adhere to the therapy regimen. Flavonoids are known to be a potential anticancer agent with an excellent safety profile. These are found to be effective preclinically against hepatocellular carcinoma through modulation of numerous pathways in hepatocarcinogenesis. But, the bioavailability issue, lack of well designed‐validated clinical evidence, the possibility of food–drug interaction etc limit its clinical utility. The research inputs mainly to overcome pharmacokinetic issues along with suitable validation of efficacy and toxicity will be a critical point for establishing flavonoids as an effective, safe, affordable therapeutics.

: Months after WHO declared COVID-19 as a Global Public Health Emergency of International Concern, it does not seem to be flattening the curve as we are still devoid of an effective vaccine and treatment modality. Amid such uncertainty, being immune is the best strategy to defend against corona attack. As the whole world is referring back to immune-boosting grandma remedies, interest is rekindled in the Indian system of Medicine, which is gifted with an abundance of herbal medicines as well as remedies. Among them, spices (root, rhizome, seed, fruit, leaf, bud, and flower of various plants used to add taste and flavors to food) are bestowed with immense medicinal potential. A plethora of clinical as well as preclinical studies reported the effectiveness of various spices for various ailments. The potential immune-boosting properties together with its excellent safety profile are making spices the current choice of Phyto-research as well as the immune-boosting home remedies during these sceptical times. The present review critically evaluates the immune impact of various Indian spices and their potential to tackle the novel coronavirus, with comments on the safety and toxicity aspects of spices.

Hepatocellular carcinoma (HCC) is one of the most common solid tumours and the second leading cause of cancer-related mortality worldwide. Advanced-recurrent HCC often requires a systemic drug therapy where multi tyrosine kinase inhibitor, sorafenib represents the first-line therapy option, but it exhibited very limited survival benefit and tumour response due to the early emergence of drug resistance and drug-related adverse effect. Immunotherapy approaches now being widely studied as an effective alternative treatment for HCC. Several immune checkpoint inhibitors (ICI) such as Nivolumab are approved as monotherapy in sorafenib resistant HCC patients. But, the existence of a plethora of immunosuppressive signals in the tumour microenvironment often leads to unsuccessful immunotherapies. In this context, combinatorial immunotherapies are getting much acceptance as a way to improve therapeutic outcome by blocking immunosuppressive signals in the tumour microenvironment. The combination of VEGF inhibitors with ICI resulted in significant synergistic effects in various preclinical and clinical studies. However, the adverse effects associated with current synthetic VEGF inhibitors limits its clinical utility. In this review, we have summarised the potential of phytochemicals especially the category of flavonoids, alkaloids, glycosides, terpenoids, and coumarin as the available-affordable-safe-effective repositories of VEGF inhibitors. Their possibilities as an alternative for synthetic VEGF inhibitors by synergistical combination with ICI is reviewed, thereby enhancing patient compliance and survival rates. This review highlights the demand for a detailed investigation of the plausible role of plant-based antiangiogenic-immunotherapy combination against HCC.

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