Cardiovascular diseases are the leading cause of death, accounting about 31% deaths globally in 2012. The major risk factors causing cardiovascular diseases are coronary atherosclerosis, hyperlipidemia, myocardial infarction, and stroke. The dominating cause of cardiovascular diseases is accredited to our modern lifestyle and diet. Medicinal plants have been used for the prevention and treatment of cardiovascular diseases from centuries. The in built chirality and chemical space of natural products have been playing an important role in providing leads and templates for pharmacophore synthesis. This review highlights one of the important naturally occurring class saponins and their role in cardioprotection along with structural characteristics and pharmacological effects such as antioxidant, Ca2+ ion regulation, antiapoptotic, antiatherosclerosis, antihyperlipidemic, hypocholesterolemic, angiogenic, vasodilatory, and hypotensive. The characteristic cholesterol lowering, hemolytic, and anticoagulant properties of the saponins prompted us to select as one of the natural products class for cardioprotection. This review covers the most updated information on saponins related to their cardioprotective effects, mechanism of action, bioavailability, and structure activity relationship.

Cholangiocarcinomas (CCA) pose a complex challenge in oncology due to diverse etiologies, necessitating tailored therapeutic approaches. This review discusses the risk factors, molecular pathology, and current therapeutic options for CCA and explores the emerging strategies encompassing targeted therapies, immunotherapy, novel compounds from natural sources, and modulation of gut microbiota. CCA are driven by an intricate landscape of genetic mutations, epigenetic dysregulation, and post-transcriptional modification, which differs based on geography (e.g., for liver fluke versus non-liver fluke-driven CCA) and exposure to environmental carcinogens (e.g., exposure to aristolochic acid). Liquid biopsy, including circulating cell-free DNA, is a potential diagnostic tool for CCA, which warrants further investigations. Currently, surgical resection is the primary curative treatment for CCA despite the technical challenges. Adjuvant chemotherapy, including cisplatin and gemcitabine, is standard for advanced, unresectable, or recurrent CCA. Second-line therapy options, such as FOLFOX (oxaliplatin and 5-FU), and the significance of radiation therapy in adjuvant, neoadjuvant, and palliative settings are also discussed. This review underscores the need for personalized therapies and demonstrates the shift towards precision medicine in CCA treatment. The development of targeted therapies, including FDA-approved drugs inhibiting FGFR2 gene fusions and IDH1 mutations, is of major research focus. Investigations into immune checkpoint inhibitors have also revealed potential clinical benefits, although improvements in survival remain elusive, especially across patient demographics. Novel compounds from natural sources exhibit anti-CCA activity, while microbiota dysbiosis emerges as a potential contributor to CCA progression, necessitating further exploration of their direct impact and mechanisms through in-depth research and clinical studies. In the future, extensive translational research efforts are imperative to bridge existing gaps and optimize therapeutic strategies to improve therapeutic outcomes for this complex malignancy.

While BCR::ABL1 tyrosine kinase inhibitors have transformed the treatment paradigm for chronic myeloid leukemia (CML), disease progression and treatment resistance due to BCR::ABL1-dependent and BCR::ABL1-independent mechanisms remain a therapeutic challenge. Natural compounds derived from plants have significantly contributed to cancer pharmacotherapy. This study investigated the efficacy of an active component of Leea indica, a local medicinal plant, in CML. Using high-performance liquid chromatography–electrospray ionization–mass spectrometry, a chemical constituent from L. indica extract was isolated and identified as gallic acid. Commercially obtained gallic acid was used as a chemical standard. Gallic acid from L. indica inhibited proliferation and induced apoptosis in CML cell lines, as did the chemical standard. Furthermore, gallic acid induced apoptosis and decreased the colony formation of primary CML CD34⁺ cells. The combination of isolated gallic acid or its chemical standard with BCR::ABL1 tyrosine kinase inhibitors resulted in a significantly greater inhibition of colony formation and cell growth compared to a single drug alone. Mechanistically, CML cells treated with gallic acid exhibited the disruption of multiple oncogenic pathways including ERK/MAPK, FLT3 and JAK/STAT, as well as impaired mitochondrial respiration. Rescue studies showed that gallic acid is significantly less effective in inducing apoptosis in mitochondrial respiration-deficient ρ⁰ cells compared to wildtype cells, suggesting that the action of gallic acid is largely through the inhibition of mitochondrial respiration. Our findings highlight the therapeutic potential of L. indica in CML and suggest that gallic acid may be a promising lead chemical constituent for further development for CML treatment.

Breast cancer and prostate cancer are the most common malignancy in women and men respectively. In view of serious side effects of the available therapies, cost of the treatment and drug-resistance, the search for more effective anticancer drug is urgently needed. Triterpenoids present in edible rhizomes of Nelumbo nucifera Gaetrn possess antiproliferative activities. To investigate the therapeutic effect of N. nucifera triterpenoids against breast and prostate cancers, the semi-synthetic derivatives of triterpenoids were prepared and monitored for their in vitro bioassay, molecular docking, QSAR and ADMET studies. Compound 2α,3β,24-triacetoxy hyptatic acid-A (3c) showed significant inhibitory activity against breast cancer (MCF-7, IC50 = 9.77 ± 0.9 μM) along with the strong binding affinity towards the active site of 3ERT with docking score of -7.2 kcal/mol. The QSAR model suggests the importance of geometrical shape and dipole moment of triterpenoids for their antiproliferative activity against MCF-7 cells, while AlogP and DPSA_1 is crucial for showing the activity against PC-3 cells. The ADMET analysis demonstrated that the triterpenoids follow most of the physicochemical properties required for their optimum bioavailability and not showing any toxicity. In this study, hyptatic acid-A emerged as a good structural template to develop novel leads against different cancers and substitution at C24 hydroxyl group has important role in bioactivity.