Identification of Natural Compounds as Inhibitors of Pyruvate Kinase M2 for Cancer Treatment.

The reliance of tumor cells on aerobic glycolysis is one of the emerging hallmarks of cancer. Pyruvate kinase M2 (PKM2), an important enzyme of glycolytic pathway, is highly expressed in a number of cancer cells. Tumor cells heavily depend on PKM2 to fulfill their divergent energetic and biosynthetic requirements, suggesting it as novel drug target for cancer therapies. Based on this context, we performed enzymatic-assay-based screening of the in-house phenolic compounds library for the identification of PKM2 inhibitors. This screening identified silibinin, curcumin, resveratrol, and ellagic acid as potential inhibitors of PKM2 with IC50 values of 0.91 µM, 1.12 µM, 3.07 µM, and 4.20 µM respectively. For the determination of Ki constants and the inhibition type of hit compounds, Lineweaver-Burk graphs were plotted. Silibinin and ellagic acid performed the competitive inhibition of PKM2 with Ki constants of 0.61 µM and 5.06 µM, while curcumin and resveratrol were identified as non-competitive inhibitors of PKM2 with Ki constants of 1.20 µM and 7.34 µM. The in silico screening of phenolic compounds against three binding sites of PKM2 provided insight into the binding pattern and functionally important amino residues of PKM2. Further, the evaluation of cytotoxicity via MTT assay demonstrated ellagic acid as potent inhibitor of cancer cell growth (IC50 = 20 µM). These results present ellagic acid, silibinin, curcumin, and resveratrol as inhibitors of PKM2 to interrogate metabolic reprogramming in cancer cells. This study has also provided the foundation for further research to validate the potential of identified bioactive entities for PKM2 targeted-cancer therapies.

Hispolon: A natural polyphenol and emerging cancer killer by multiple cellular signaling pathways.

Nature as an infinite treasure of chemotypes and pharmacophores will continue to play an imperative role in the drug discovery. Natural products (NPs) such as plant and fungal metabolites have emerged as leads in drug discovery during recent years due to their efficacy, safety and selectivity. The current review summarizes natural sources as well as pharmacological potential of hispolon which is a major constituent of traditional medicinal mushroom Phellinus linteus. The study aims to update the scientific community about recent developments of hispolon in the arena of natural drugs by providing insights into its present status in therapeutic pursuits. Hispolon, a polyphenol has been reported to possess anticancer, antidiabetic, antioxidant, antiviral and anti-inflammatory activities. It fights against cancer via induction of apoptosis, halting cell cycle and inhibition of metastasis by targeting various cellular signaling pathways including PI3K/Akt, MAPK and NF-κB. The current review proposes that hispolon provides a novel opportunity for pharmacological applications and its styrylpyrone carbon skeleton might serve as an attractive scaffold for drug development. However, future researches are recommended to assess bioavailability, toxicological limits, pharmacokinetic and pharmacodynamic profiles of hispolon, in order to establish its potential as a potent multi-targeted drug in the near future.

Eupatilin: a natural pharmacologically active flavone compound with its wide range applications.

Eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone) is a pharmacologically active flavone which has been isolated from a variety of medicinal plants. Eupatilin is known to possess various pharmacological properties such as anti-cancer, anti-oxidant, and anti-inflammatory. It is speculated that eupatilin could be subjected to structural optimization for the synthesis of derivative analogs to reinforce its efficacy, to minimize toxicity, and to optimize absorption profiles, which will ultimately lead towards potent drug candidates. Although, reported data acclaim multiple pharmacological activities of eupatilin but further experimentations on its molecular mechanism of action are yet mandatory to elucidate full spectrum of its pharmacological activities.

Secreted frizzled-related protein 4 and its implication in obesity and type-2 diabetes.

Secreted frizzled-related protein 4 (SFRP4) is a member of secreted protein family with sequence similarity to frizzled receptors of wingless-related integration site (Wnt) signaling pathways. These proteins control diverse functions from embryonic development to adults in many organisms including humans. Initially, SFRPs were recognized as antagonists of Wnt signaling and supposed to interact with Wnts. Further research demonstrated their interactions to frizzled receptors and a functional diversity was related to these proteins, Wnt signaling potentiation in addition to modulation. SFRP4 is the largest member of SFRP family and is implicated in many diseases including obesity, type 2 diabetes (T2D), and cancer. SFRP4 acts as a biomarker for T2D and was expressed several years before clinical diagnosis of disease. This review mainly focusses on the role of SFRP4 in obesity and how it can lead to ß-cell failure and ultimately to T2D. The role of SFRP4 in adipose tissues causing increased production of adipokines lead to the oxidative stress in pancreas that particularly have low amount of antioxidant enzymes in pancreatic ß-cells leading to failure in exocytosis of insulin containing granules causing T2D. Obesity-induced inflammation is a principal factor in pathogenesis of insulin resistance as well as metabolic syndrome. Pro-inflammatory cytokines have potential to cause insulin resistance in skeletal muscles, adipose tissue, and liver via inhibition of insulin signal transduction. Secretion of SFRP4 is mediated by interleukin 1-ß (IL1-ß). This review highlights the molecular mechanisms by which SFRP4 leads to T2D. Understanding of molecular mechanism and targeting SFRP4 could help to eradicate or reduce chances of developing T2D.

Phosphoglycerate mutase 1 in cancer: A promising target for diagnosis and therapy.

Altered enzymatic machineries are a substantial biochemical characteristic of tumor cell metabolism that switch metabolic profile from oxidative phosphorylation to amplified glycolysis as well as increased lactate production under hypoxia conditions. Reprogrammed metabolic profile is an emerging hallmark of cancer. Overexpression of several glycolytic enzymes and glucose transporters has been reported in 24 different types of cancers that represent approximately 70% of all the cancer cases around the globe. Thus, targeting glycolytic enzymes could serve as tempting avenue for drug design against cancer. Phosphoglycerate mutase 1 (PGAM1) is an important glycolytic enzyme that catalyzes the conversion of 3-phosphoglycerate to 2-phosphoglycerate. Recent investigations have revealed the overexpression of PGAM1 in several human cancers that is linked with tumor growth, survival, and invasion. The aim of this review is to update scientific research network with cancer-specific role of PGAM1 to elucidate its capability as bonafide therapeutic target for cancer therapy. Moreover, we have also summarized the reported genetic and pharmacological inhibitors of PGAM1. This study suggests that further investigations on PGAM1 should focus on the exploration of molecular mechanisms of PGAM1 overexpression in development of cancer, assessment of biosafety profiles of known inhibitors of PGAM1, and utilization of PGAM1 inhibitors in combinatorial therapies. These future studies will surely support the unbiased strategies for the development of novel PGAM1 inhibitors for cancer therapies.

Eriocalyxin B induces apoptosis in human triple negative breast cancer cells via inhibiting STAT3 activation and mitochondrial dysfunction.

Eriocalyxin B (EriB), a potent ent-kaurene extracted from Isodon eriocalyx, has turned up as novel anti-cancer agent during recent years against a range of cancer types. TNBC (Triple negative breast cancer) is highly aggressive breast cancer, which is resistant towards current therapeutics due to absence of drug targets. Here, we have probed the molecular mechanism of EriB-induced apoptosis in TNBC (MDA-MB231) cells to check whether its anticancer activity is mediated by modulation of STAT3 and NF-Ï°B. EriB induced apoptosis in MDA-MB231 cells via inhibiting NF-Ï°Bp65, STAT3 phosphorylation, increasing Bax/Bcl-2 ratio, MMP dissipation, and activation of caspase-3. These results provide a rationale for further in vivo investigations on EriB, which might also prove to be a potential drug candidate for developing novel therapeutics against TNBC.

Hispolon induces apoptosis against prostate DU145 cancer cells via modulation of mitochondrial and STAT3 pathways.

Hispolon, a bioactive polyphenolic entity extracted from Phellinus linteus, possesses anticancer, antiinflammatory and anti-oxidant properties. Despite the reported therapeutic effects of this natural chemical entity, inhibitory potential of hispolon towards prostate carcinoma DU145 cells and mechanism of its action are yet to be explicated. Deregulated STAT3 pathway performs multifaceted functions in facilitating the development of cancer. Here, we have investigated the mechanism of hispolon by which it exerts its anticancer effects in DU145 cells and whether its anticancer activity is mediated by modulation of STAT3. Our outcomes show that hispolon significantly halted the multiplication of DU145 cells as well as arrested cell cycle at S phase. S phase arrest induced by hispolon was associated with downregulation of cyclin B1, cyclin D1 and CDK4 while up-regulation of p21. Moreover, hispolon treatment leads towards induction of apoptosis in a dose-dependent mode in DU145 cells. Hispolon induced modulation of Bcl-2 family proteins lead towards loss of MMP allowing the discharge of cytochrome c from mitochondrial porin channels which triggered the cascade of caspases ultimately causing cellular death. We further investigated the role of hispolon in mediating deregulated STAT3 pathways in DU145 cells. Hispolon has potential to downregulate the p-STAT3 expression with no effect on total STAT3. Contemporaneously, these results represent that hispolon's anticancer mechanism of action proceeds via downregulating the phosphorylation of STAT3 and induction of apoptosis via mitochondrial pathway.

Neurada procumbens promotes functions regain in a mouse model of mechanically induced sciatic nerve injury.

Peripheral nerve injury is a complex condition which results in restricted physical activity. Despite the tremendous efforts to figure out effective remedies, the complete functional retrieval is still a goal to be achieved. So, the need of hour is the exploration of potential natural compounds to recover this functional loss. Here, we have investigated the role of a local plant "Neurada procumbens" in ameliorating the functional recovery after an induced nerve compression injury in a mouse model. A dose of N. procumbens (50mg/kg of body weight) was administered orally from the day of injury to onwards. The motor functional recovery was assessed by evaluating muscle grip strength and sciatic functional index; while the sensory functions were gauged by the hotplate test. The serological parameters were carried out to analyze the effect of N. procumbens on oxidative stress level. The recovery of sensory and motor functions was significantly improved and perceived earlier in the treatment group. Moreover, the elevated antioxidant level was statistically significant in the treatment group. These results indicate that the supplementation of N. procumbens accelerates functional recovery after sciatic nerve crush injury.

Malic enzyme 2 as a potential therapeutic drug target for cancer.

Reprogrammed metabolic profile is a biochemical fingerprint of cancerous cells, which represents one of the "hallmarks of cancer." The aberrant expression pattern of enzymatic machineries orchestrates metabolic activities into a platform that ultimately promotes cellular growth, survival, and proliferation. The NADP(+)-dependent mitochondrial malic enzyme 2 (ME2) has been widely appreciated due to its function as a provider of pyruvate and reducing power to the cell for biosynthesis of fatty acids and nucleotides along with maintenance of redox balance. Multiple lines of evidences have indicated that ME2 is a bonafide therapeutic target and novel biomarker which plays critical role during tumorigenesis. The objective of this review is to provide an update on the cancer-specific role of ME2 in order to explore its potential for therapeutic opportunities. Furthermore, we have discussed the potential of genetic and pharmacological inhibitors of ME2 in the light of previous research work for therapeutic advancements in cancer treatment. It is contemplated that additional investigations should focus on the use of ME2 inhibitors in combinational therapies as rational combinations of metabolic inhibitors and chemotherapy may have the ability to cure cancer. © 2018 IUBMB Life, 70(11):1076-1083, 2018.

Determination of anti-oxidative, anti-microbial activity and heavy metal contents of Leucoagaricus leucothites.

Mushrooms, a treasure of diverse bioactive scaffolds, have been widely admired due to their nutritional and medicinal significance all over the world. The current study intended to evaluate the therapeutic potentiality of an edible mushroom, Leucoagaricus leucothites (Vittad.) Wasser. Thus, anti-oxidant potential of L. leucothites was determined using DPPH assay and for the determination of anti-microbial potential agar dilution procedure was followed. TOS (total oxidant status), TAS (total anti-oxidant status), and OSI (oxidative stress index) values were evaluated utilizing Rel Assay Kits. For the assessment of heavy metal contents, wet decomposition approach with atomic absorption spectrophotometry was adopted. Screening of phytochemicals present in ethanolic extract of L. leucothites were determined by HPLC. TAS, TOS and OSI values were found to be 8.291mmol/L, 10.797µmol/L and 0.130 respectively. Our results declared that heavy metal contents are generally in the safe range. Phytochemical analysis of L. leucothites has affirmed the presence of important phenolics such as gallic acid, catechin, and hesperidin. Investigations on anti-oxidant and anti-microbial potential of L. leucothites has uncovered the fact that this naturally occurring, biologically active, and therapeutically effective mushroom specie has natural borne anti-oxidant and anti-microbial potential and it would be worthwhile to use it for nutritional as well as medicinal purpose.

Ameliorating role of methanolic leaves extract of Fraxinus xanthoxyloides against CCl4-challanged nephrotoxicity in rats.

Roots, bark, stem/twigs, and leaves of Fraxinus xanthoxyloides are being used regionally for the cure of malaria, jaundice, internal injuries, pneumonia, pain, rheumatism and also in fracture of bones. Our objective was to assess the methanolic leaves extract of F. xanthoxyloides for its antioxidant capability against oxidative stress induced by carbon tetrachloride (CCl4) in the kidney of Sprague-Dawley rats. Duration of this experiment was 30 days and doses were given on alternative days. Urine of rats was assessed for kidney function and renal tissues for antioxidant enzymes activity, biochemical markers, comet assay and histopathology. Enhanced urinary creatinine, urobilinogen levels and decreased creatinine clearance, protein contents, and albumin levels were observed by CCl4 administration when matched to controls. CCl4 injection also decreased the level of reduced glutathione, catalase, super oxide dismutase, peroxidase, glutathione s-transferase, glutathione reductase, and tissue protein while elevated the levels of thiobarbituric acid reactive substances, DNA damages and H2O2 in renal tissues of experimental animals. Co-treatment of FXM and silymarin, lead to the restoration of all the above tested parameters of kidney. Through this study we affirmed the ameliorating role of F. xanthoxyloides in oxidative stress affiliated disorders of kidney.

Multidimensional in silico strategy for identification of natural polyphenols-based SARS-CoV-2 main protease (Mpro) inhibitors to unveil a hope against COVID-19.

SARS-CoV-2, a rapidly spreading new strain of human coronavirus, has affected almost all the countries around the world. The lack of specific drugs against SARS-CoV-2 is a significant hurdle towards the successful treatment of COVID-19. Thus, there is an urgent need to boost up research for the development of effective therapeutics against COVID-19. In the current study, we investigated the efficacy of 81 medicinal plant-based bioactive compounds against SARS-CoV-2 Mpro by using various in silico techniques. The interaction affinities of polyphenolic compounds towards SARS-CoV-2 Mpro was assessed via intramolecular (by Quantum Mechanic), intermolecular (by Molecular Docking), and spatial (by Molecular Dynamic) simulations. Our obtained result demonstrate that Hesperidin, rutin, diosmin, and apiin are most effective compounds agents against SARS-CoV-2 Mpro as compared to Nelfinavir (positive control). This study will hopefully pave a way for advanced experimental research to evaluate the in vitro and in vivo efficacy of these compounds for the treatment of COVID-19.

A Review on Phyto-pharmacology of Oxalis corniculata.

Oxalis corniculata (Oxalidaceae) is a small decumbent and delicate appearing medicinal herb flourishing in warm temperate and tropical domains such as Pakistan and India. Main bioactive chemical constituents of Oxalis plant include several alkaloids, flavonoids, terpenoids, cardiac glycosides, saponins, and phlobatannins, along with steroids. Due to its polyphenolic, glycosides and flavonoid profile, it is proved to be protective in numerous ailments and exhibit various biological activities such as anti-fungal, anti-cancer, anti-oxidant, antibacterial, anti-diabetic, and cardioprotective. Moreover, bioactive phytochemicals from this plant possess significant wound healing potential. Our current effort intends to emphasize on the immense significance of this plant species, which have not been the subject matter of clinical trials and effective pharmacological studies, even though its favored usage has been stated. This review proposes that Oxalis corniculata possess a potential for the cure of various diseases. However, further researches on isolation and characterization of bioactive compounds along with pre-clinical trials are compulsory to figure out its pharmacological applications.

Radioprotective Role of Natural Polyphenols: From Sources to Mechanisms.

The identification and development of radioprotective agents have emerged as a subject matter of research during recent years due to the growing usage of ionizing radiation in different areas of human life. Previous work on synthetic radioprotectors has achieved limited progress because of the numerous issues associated with toxicity. Compounds extracted from plants have the potential to serve as lead candidates for developing ideal radioprotectors due to their low cost, safety, and selectivity. Polyphenols are the most abundant and commonly dispersed group of biologically active molecules possessing a broad range of pharmacological activities. Polyphenols have displayed efficacy for radioprotection during various investigations and can be administered at high doses with lesser toxicity. Detoxification of free radicals, modulating inflammatory responses, DNA repair, stimulation of hematopoietic recovery, and immune functions are the main mechanisms for radiation protection with polyphenols. Epicatechin, epigallocatechin-3-gallate, apigenin, caffeic acid phenylethylester, and silibinin provide cytoprotection together with the suppression of many pro-inflammatory cytokines owing to their free radical scavenging, anti-oxidant, and anti-inflammatory properties. Curcumin, resveratrol, quercetin, gallic acid, and rutin's radioprotective properties are regulated primarily by the direct or indirect decline in cellular stress. Thus, polyphenols may serve as potential candidates for radioprotection in the near future; however, extensive investigations are still required to better understand their protection mechanisms.

Caffeic acid derivatives (CAFDs) as inhibitors of SARS-CoV-2: CAFDs-based functional foods as a potential alternative approach to combat COVID-19.

BACKGROUND: SARS-CoV-2, an emerging strain of coronavirus, has affected millions of people from all the continents of world and received worldwide attention. This emerging health crisis calls for the urgent development of specific therapeutics against COVID-19 to potentially reduce the burden of this emerging pandemic. PURPOSE: This study aims to evaluate the anti-viral efficacy of natural bioactive entities against COVID-19 via molecular docking and molecular dynamics simulation. METHODS: A library of 27 caffeic-acid derivatives was screened against 5 proteins of SARS-CoV-2 by using Molegro Virtual Docker 7 to obtain the binding energies and interactions between compounds and SARS-CoV-2 proteins. ADME properties and toxicity profiles were investigated via www.swissadme.ch web tools and Toxtree respectively. Molecular dynamics simulation was performed to determine the stability of the lead-protein interactions. RESULTS: Our obtained results has uncovered khainaoside C, 6-O-Caffeoylarbutin, khainaoside B, khainaoside C and vitexfolin A as potent modulators of COVID-19 possessing more binding energies than nelfinavir against COVID-19 Mpro, Nsp15, SARS-CoV-2 spike S2 subunit, spike open state and closed state structure respectively. While Calceolarioside B was identified as pan inhibitor, showing strong molecular interactions with all proteins except SARS-CoV-2 spike glycoprotein closed state. The results are supported by 20 ns molecular dynamics simulations of the best complexes. CONCLUSION: This study will hopefully pave a way for development of phytonutrients-based antiviral therapeutic for treatment or prevention of COVID-19 and further studies are recommended to evaluate the antiviral effects of these phytochemicals against SARS-CoV-2 in in vitro and in vivo models.

Furanodiene: A Novel, Potent, and Multitarget Cancer-fighting Terpenoid.

Natural products have served as a limitless reservoir of bioactive scaffolds for drug discovery against several disorders. Furanodiene is a bioactive natural product isolated from several plants of genus Curcuma. Its therapeutic potential against cancer, inflammation, and angiogenesis has been well-documented. The current review is an update about the natural sources and anti-cancer action mechanism of furanodiene. Furanodiene exerts its anti-cancer effects via induction of apoptosis in several cancer types by modulating MAPKs/ERK, NF-κB, and Akt pathways. Furanodiene has been systematically studied for its anti-cancer potential. However, pharmacokinetics, pharmacodynamics, pre-clinical and clinical studies still needed to be conducted to completely validate the potential of furanodiene for the treatment of cancer.

Jaceosidin: A Natural Flavone with Versatile Pharmacological and Biological Activities.

Nature always remains an inexhaustible source of treasures for mankind. It remains a mystery for every challenge until the completion of the challenge. While we talk about the complicated health issues, nature offers us a great variety of chemical scaffolds and their various moieties packed in the form of natural products e.g., plants, microorganisms (fungi, algae, protozoa), and terrestrial vertebrates and invertebrates. This review article is an update about jaceosidin, a bioactive flavone, from genus Artemisia. This potentially active compound exhibits a variety of pharmacological activities including anti-inflammatory, anti-oxidant, anti-bacterial, antiallergic and anti-cancer activities. The bioactivities and the therapeutic action of jaceosidin, especially the modulation of different cell signaling pathways (ERK1/2, NF-κB, PI3K/Akt and ATM-Chk1/2) which become deregulated in various pathological disorders, have been focused here. The reported data suggest that the bioavailability of this anti-cancer compound should be enhanced by utilizing various chemical, biological and computational techniques. Moreover, it is recommended that researchers and scientists should work on exploring the mode of action of this particular flavone to precede it further as a potent anti-cancer compound.

Mangifera indica Extracts as Novel PKM2 Inhibitors for Treatment of Triple Negative Breast Cancer.

Pyruvate kinase (PK), a key enzyme that determines glycolytic activity, has been known to support the metabolic phenotype of tumor cells, and specific pyruvate kinase isoform M2 (PKM2) has been reported to fulfill divergent biosynthetic and energetic requirements of cancerous cells. PKM2 is overexpressed in several cancer types and is an emerging drug target for cancer during recent years. Therefore, this study was carried out to identify PKM2 inhibitors from natural products for cancer treatment. Based on the objectives of this study, firstly, plant extract library was established. In order to purify protein for the establishment of enzymatic assay system, pET-28a-HmPKM2 plasmid was transformed to E. coli BL21 (DE3) cells for protein expression and purification. After the validation of enzymatic assay system, plant extract library was screened for the identification of inhibitors of PKM2 protein. Out of 51 plant extracts screened, four extracts Mangifera indica (leaf, seed, and bark) and Bombex ceiba bark extracts were found to be inhibitors of PKM2. In the current study, M. indica (leaf, seed, and bark) extracts were further evaluated dose dependently against PKM2. These extracts showed different degrees of concentration-dependent inhibition against PKM2 at 90-360 µg/ml concentrations. We have also investigated the anticancer potential of these extracts against MDA-MB231 cells and generated dose-response curves for the evaluation of IC50 values. M. indica (bark and seed) extracts significantly halted the growth of MDA-MB231 cells with IC50 values of 108 µg/ml and 33 µg/ml, respectively. Literature-based phytochemical analysis of M. indica was carried out, and M. indica-derived 94 compounds were docked against three binding sites of PKM2 for the identification of PKM2 inhibitors. The results of in silico based screening have unveiled various PKM2 modulators; however, further studies are recommended to validate their PKM2 inhibitory potential via in vitro biochemical assay. The results of this study provide novel findings for possible mechanism of action of M. indica (bark and seed) extracts against TNBC via PKM2 inhibition suggesting that M. indica might be of therapeutic interest for the treatment of TNBC.

Physcion and Physcion 8-O-ß-D-glucopyranoside: Natural Anthraquinones with Potential Anticancer Activities.

Nature has provided prodigious reservoirs of pharmacologically active compounds for drug development since times. Physcion and physcion 8-O-ß-D-glucopyranoside (PG) are bioactive natural anthraquinones which exert anti-inflammatory and anticancer properties with minimum or no adverse effects. Moreover, physcion also exhibits anti-microbial and hepatoprotective properties, while PG is known to have anti-sepsis as well as ameliorative activities against dementia. This review aims to highlight the natural sources and anticancer activities of physcion and PG, along with associated mechanisms of actions. On the basis of the literature, physcion and PG regulate multitudinous cell signaling pathways through the modulation of various regulators of cell cycle, protein kinases, microRNAs, transcriptional factors, and apoptosis linked proteins resulting in the effective killing of cancerous cells in vitro as well as in vivo. Both compounds effectively suppress metastasis, furthermore, physcion acts as an inhibitor of 6PGD and also plays an important role in chemosensitization. This review article suggests that physcion and PG are potent anticancer drug candidates, but further investigations on their mechanism of action and pre-clinical trials are mandatory in order to comprehend the full potential of these natural cancer killers in anticancer remedies.

Osthole: A Multifunctional Natural Compound with Potential Anticancer, Antioxidant and Anti-inflammatory Activities.

Nature has always proved to be a significant reservoir of bioactive scaffolds that have been used for the discovery of drugs since times. Medicinal plants continue to be a solid niche for biologically active and therapeutically effective chemical entities, opening up new avenues for the successful treatment of several human diseases. The contribution of plant-derived compounds to drug discovery, either in their original or in the semi-synthetic derivative form, extends far back in time. This review aims to focus on the sources, biological, and pharmacological profile of a pharmacologically active plant-derived coumarin, osthole, which is an important component of numerous remedial plants such as Cnidium monnieri. Several studies have revealed that osthole possess pharmacological properties such as anticancer, antioxidant, anti-hyperglycemic, neuroprotective, and antiplatelet. Osthole has been reported to regulate various signaling pathways, which in turn modulate several apoptosis-related proteins, cell cycle regulators, protein kinases, transcriptional factors, cytokines, and growth receptors affiliated with inflammation, proliferation and several other ailments. Osthole is known to halt proliferation and metastasis of cancerous cells by arresting the cell cycle and inducing apoptosis. The data in this review paper supports the pharmacological potential of osthole but further experimentation, biosafety profiling and synergistic effects of this compound need to be focused by the researchers to understand the full spectrum of pharmacological potential of this therapeutically potent compound.