Current Drug Targets - Online First

Obesity is a significant health concern due to its rapid increase worldwide. It has been linked to the pathogenic factors of renal diseases, cancer, cardiovascular diseases, hypertension, dyslipidemia, and type 2 diabetes. Notably, obesity raises the likelihood of developing chronic kidney disease (CKD), leading to higher adult mortality and morbidity rates. This study explores the molecular mechanisms that underlie obesity-associated nephropathy and its clinical implications. Obesity-Associated Nephropathy (OAN) develops and worsens due to insulin resistance and hyperinsulinemia, which promote renal sodium reabsorption, glomerular hyperfiltration, and hypertension, leading to progressive kidney damage. Renal damage is further aggravated by persistent inflammation and redox damage, mediated by adipokines and proinflammatory cytokines, such as TNF-α and IL-6. Furthermore, stimulation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) intensifies glomerular hypertension and fibrosis. These elements cause glomerular hyperfiltration, renal hypertrophy, and progressive kidney damage. Clinical manifestations of obesity-associated nephropathy include proteinuria, reduced glomerular filtration rate (GFR), and ultimately, CKD. Management strategies currently focus on lifestyle modifications, such as weight loss through diet and exercise, which have been effective in reducing proteinuria and improving GFR. Pharmacological treatments targeting metabolic pathways, including GLP-1 receptor agonists and SGLT2 inhibitors, have shown renoprotective properties. Additionally, traditional RAAS inhibitors offer therapeutic benefits. Early detection and comprehensive management of OAN are essential to prevent its progression and lessen the burden of CKD.

The second largest cause of cancer-related death worldwide, Hepatocellular Carcinoma (HCC) is also the most common primary liver cancer. HCC typically arises in patients with liver cirrhosis. Existing synthetic medicines for treating chronic liver disease are ineffective and come with undesirable side effects. Although herbal remedies have widespread popularity, there is still a long road ahead before they are fully accepted by the scientific community. Secondary metabolites and phytochemicals found in plants are abundant in both the human diet and the non-human environment. Natural plant chemicals have been shown to be beneficial as therapeutic and chemopreventive treatments for a wide variety of chronic disorders. Many diseases, including HCC, can be effectively treated with the help of phytochemicals found in food. Resveratrol, curcumin, urolithin A, silibinin, quercetin, N-trans-feruloyl octopamine, emodin, lycopene, caffeine, and phloretin are all examples. Approximately, 60% of all anticancer medications are determined to be derived from natural substances, according to recent studies. Plant derivatives have played an important role in cancer due to their capacity to scavenge free radicals, limit cell proliferation, and set off apoptosis. The progression of HCC is linked to inflammatory signaling pathways, and this study sought to look at how novel approaches, such as phytomedicines, are being used to fight cancer. Recent advancements in molecular mechanisms and drug targeting for HCC have been discussed in this review.