Histone deacetylases (HDACs) are enzymes that play a role in chromatin remodeling and epigenetics. They belong to a specific category of enzymes that eliminate the acetyl part of the histones’ -N-acetyl lysine, causing the histones to be wrapped compactly around DNA. Numerous biological processes rely on HDACs, including cell proliferation and differentiation, angiogenesis, metastasis, gene regulation, and transcription. Epigenetic changes, specifically increased expression and activity of HDACs, are commonly detected in cancer. As a result, HDACi could be used to develop anticancer drugs. Although preclinical outcomes with HDACs as monotherapy have been promising clinical trials have had mixed results and limited success. In both preclinical and clinical trials, however, combination therapy with different anticancer medicines has proved to have synergistic effects. Furthermore, these combinations improved efficacy, decreased tumor resistance to therapy, and decreased toxicity. In the present review, the detailed modes of action, classification of HDACs, and their correlation with different cancers like prostate, breast, and ovarian cancer were discussed. Further, the different cell signaling pathways and the structure-activity relationship and pharmaco-toxicological properties of the HDACi, and their synergistic effects with other anticancer drugs observed in recent preclinical and clinical studies used in combination therapy were discussed for prostate, breast, and ovarian cancer treatment.

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Hesperidin has gained major interest recently due to the outbreak of COVID-19. The traction has led to more research being conducted on the compound Hesperidin. Recent studies have shown its anti-inflammatory and anti-viral attributes which have beneficial effects on severe acute respiratory syndrome (SARS-CoV-2). Hesperidin has also shown unique effects on the protein of SARS-CoV-2, which lead to a good preventative measure for SARS-CoV-2. Hesperidin also causes a suppression of appetite which helps to combat obesity through the release of Cholecystokinin. Furthermore, Hesperidin has shown cardioprotective properties, which cause an increase in plasma high-density lipoprotein levels and a decrease in plasma low-density lipoprotein levels. Hesperidin is also used in combination with the Japanese herb Rikkunshito, which has shown potential in a discovery of a new drug for gastrointestinal motility as hesperidin can depolarize pacemaker potential in interstitial cells of Cajal (ICC). The chemo-preventive effect of Hesperidin is caused by its antioxidant effect which may prevent tissue necrosis due to oxidative stress. Hesperidin’s photo-protective effect can reduce the damage to the skin caused by UV rays. Hesperidin also possesses wound-healing properties.

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