Dharambir Kashyap

Cordycepin: A bioactive metabolite with therapeutic potential

Cytotoxic nucleoside analogues were the first chemotherapeutic agents for cancer treatment. Cordycepin, an active ingredient of the insect fungus Cordyceps militaris, is a category of compounds that exhibit significant therapeutic potential. Cordycepin has many intracellular targets, including nucleic acid (DNA/RNA), apoptosis and cell cycle, etc. Investigations of the mechanism of anti-cancer drugs have yielded important information for the design of novel drug targets in order to enhance anti-tumor activity with less toxicity to patients. This extensive review covers various molecular aspects of cordycepin interactions with its recognized cellular targets and proposes the development of novel therapeutic strategies for cancer treatment.

Ursolic acid (UA): A metabolite with promising therapeutic potential.

Plants are known to produce a variety of bioactive metabolites which are being used to cure various life threatening and chronic diseases. The molecular mechanism of action of such bioactive molecules, may open up new avenues for the scientific community to develop or improve novel therapeutic approaches to tackle dreadful diseases such as cancer and cardiovascular and neurodegenerative disorders. Ursolic acid (UA) is one among the categories of such plant-based therapeutic metabolites having multiple intracellular and extracellular targets that play role in apoptosis, metastasis, angiogenesis and inflammatory processes. Moreover, the synthetic derivatives of UA have also been seen to be involved in a range of pharmacological applications, which are associated with prevention of diseases. Evidences suggest that UA could be used as a potential candidate to develop a comprehensive competent strategy towards the treatment and prevention of health disorders. The review article herein describes the possible therapeutic effects of UA along with putative mechanism of action.

Molecular mechanisms of action of quercetin in cancer: recent advances.

In the last few decades, the scientific community has discovered an immense potential of natural compounds in the treatment of dreadful diseases such as cancer. Besides the availability of a variety of natural bioactive molecules, efficacious cancer therapy still needs to be developed. So, to design an efficacious cancer treatment strategy, it is essential to understand the interactions of natural molecules with their respective cellular targets. Quercetin (Quer) is a naturally occurring flavonol present in many commonly consumed food items. It governs numerous intracellular targets, including the proteins involved in apoptosis, cell cycle, detoxification, antioxidant replication, and angiogenesis. The weight of available synergistic studies vigorously fortifies the utilization of Quer as a chemoprevention drug. This extensive review covers various therapeutic interactions of Quer with their recognized cellular targets involved in cancer treatment.

Molecular aspects of metal oxide nanoparticle (MO-NPs) mediated pharmacological effects.

Metal oxide nanoparticles (MO-NPs) are the multidisciplinary nano-scaled molecules which are being used in the diagnosis and treatment of the challenging diseases including cancer. Evidence suggest that antimicrobial formulations in the form of MO-NPs can be possibly used as effective antimicrobial agents. In addition, MO-NPs are known to target various cellular signaling pathways associated with apoptosis, angiogenesis, metastasis and inflammation of cancer. In combination with other chemotherapeutic/anticancer agents, MO-NPs not only increase their bioavailability and efficacy but also lower down the requirement of active dosages. To date, to our knowledge there is no single comprehensive report on cellular and molecular interactions of MO-NPs which have been well elaborated in this review. Also we highlight various action mechanisms through which MO-NPs act as antimicrobial, anticancer, antioxidant and anti-inflammatory agents.

Molecular aspects of melatonin (MLT)-mediated therapeutic effects

Hormones are a class of molecules, which mediate their effects by regulating a variety of signalling pathways. Melatonin (N-acetyl-5-methoxytryptamine), a pineal gland hormone, is one among the categories of compounds having various therapeutic and pharmacological effects. Melatonin has many intracellular as well as extracellular targets including apoptosis, metastasis, angiogenesis and inflammatory pathways. Gene-profile studies have further established its antagonist effect on the various genes involved in the tumour progression, neurodegeneration and ageing. It has also been known to reduce the toxicity induced by chemotherapeutic agents in advanced stages of tumour. The present review extensively describes the molecular interactions of melatonin with various recognized cellular targets, which may lead the scientific community to propose novel therapeutic strategies.

Molecular targets of gambogic acid in cancer: recent trends and advancements

Natural compounds have been known as biosafety agents for their significant clinical and biological activity against dreadful diseases, including cancer, cardiovascular, and neurodegenerative disorders. Gambogic acid (GA), a naturally occurring xanthone-based moiety, reported from Garcinia hanburyi tree, is known to perform numerous intracellular and extracellular actions, including programmed cell death, autophagy, cell cycle arrest, antiangiogenesis, antimetastatic, and anti-inflammatory activities. In addition, GA-based synergistic approaches have been proven to enhance the healing strength of existing chemotherapeutic agents along with lesser side effects. The present review uncovers the bio-therapeutic potential of gambogic acid along with the possible mechanistic interactions of GA with its recognized cellular targets.

Kaempferol – A dietary anticancer molecule with multiple mechanisms of action: Recent trends and advancements

Abstract The consumption of diet-based naturally bioactive metabolites is preferred to synthetic material in order to avert health-associated disorders. Among the plant-derived polyphenols, kaempferol (KMF) is considered as a valuable functional food ingredient with a broad range of therapeutic applications such as anti-cancer, antioxidant and anti-inflammatory uses. KMF acts on a range of intracellular as well as extracellular targets involved in the cell signaling pathways that in turn are known to regulate the hallmarks of cancer growth progressions like apoptosis, cell cycle, invasion or metastasis, angiogenesis and inflammation. Importantly, the understanding of mechanisms of action of KMF-mediated therapeutic effects may help the scientific community to design novel strategies for the treatment of dreadful diseases. The current review summarizes the various types of molecular targets of KMF in cancer cells as well as other health-associated disorders. In addition, this review also highlights the absorption, metabolism and epidemiological findings.

Ursolic Acid and Oleanolic Acid: Pentacyclic Terpenoids with Promising Anti-Inflammatory Activities.

BACKGROUND Plant derived products are not only served as dietary components but also used to treat and prevent the inflammatory associated diseases like cancer. Among the natural products pentacyclic terpenoids including ursolic acid and oleanolic acid are considered as the promising anti-inflammatory therapeutic agents. OBJECTIVES The current review extensively discusses the anti-inflammatory therapeutic potential of these pentacyclic moieties along with their proposed mechanisms of action. Furthermore, the relevant patents have also been listed to present the health benefits of these promising therapeutic agents to pin down the inflammatory diseases. Expert opinion: Pentacyclic terpenoids are known to negatively down-regulate a variety of extracellular and intracellular molecular targets associated with disease progression. The major anti-inflammatory effects of these molecules have been found to be mediated via inactivation of NFkB, STAT3/6, Akt/mTOR pathways. A number of patents on UA & OA based moieties have been reported between 2010 and 2016. Still there have been only a few compounds which meet the need of sufficient hydro solubility and bioavailability along with higher anti-inflammatory activities. Thus, it is essential to develop novel derivatives of terpenpoids which may not only overcome the solubility issues but also may improve their therapeutic effects. In addition, scientific community may utilize nanotechnology based drug delivery systems so as to increase the bio-availability, selectivity and dosages related problems.

Mechanistic insight into carnosol-mediated pharmacological effects: Recent trends and advancements

&NA; For several decades, bioactive phytochemicals have been appreciated to prevent and cure various lethal diseases. Many studies have proven the ability of dietary phytochemicals to avoid and retard tumor initiation and progression. Among the pharmacologically active moieties, terpenoids are considered one of the most important classes. Carnosol, is also a kind of diterpenoid, which known to possess a range of therapeutic effects such as anti‐cancer, anti‐inflammatory, and anti‐oxidant activities. All these effects are mediated via modulating different signaling cascades, including apoptosis regulating molecules (Bax/Bcl2), prosurvival‐proproliferative molecules (Akt/mTOR, MAPK), transcription factors like NF‐kappaB, STAT3‐6, and steroid receptors, such as androgen and estrogen receptors. The present review highlights the recent trends and advancements have been done in the field of research by using carnosol. Graphical abstract Figure. No caption available.

Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy

&NA; A wide variety of chronic diseases, such as neurodegenerative and cardiovascular disorders, diabetes mellitus, osteoarthtitis, obesity and various cancers, are now being treated with cost effective phytomedicines. Since synthetic medicines are very expensive, concerted efforts are being made in developing and poor countries to discover cost effective medicines for the treatment of non‐communicable diseases (NCDs). Understanding the underlying mechanisms of bioactive medicines from natural sources would not only open incipient avenues for the scientific community and pharmaceutical industry to discover new drug molecules for the therapy of NCDs, but also help to garner knowledge for alternative therapeutic approaches for the management of chronic diseases. Fisetin is a polyphenolic molecule of flavonoids class, and belongs to the bioactive phytochemicals that have potential to block multiple signaling pathways associated with NCDs such as cell division, angiogenesis, metastasis, oxidative stress, and inflammation. The emerging evidence suggests that fisetin may be useful for the prevention and management of several types of human malignancies. Efforts are being made to enhance the bioavailability of fisetin after oral administration to prevent and/or treat cancer of the liver, breast, ovary and other organs. The intent of this review is to highlight the in vitro and in vivo activities of fisetin and to provide up‐to‐date information about the molecular interactions of fisetin with its cellular targets involved in cancer initiation, promotion and progression as well as to focus on strategies underway to increase the bioavailability and reduce the risk of deleterious effects, if any, associated with fisetin administration. Graphical abstract: Figure. No caption available.