Quantification of Tissue-Specific Paclitaxel in Himalayan Yew Using HPTLC-Densitometric Analysis, Assessment of Toxicological Activity, and Tissue-Specific Evaluation of Antioxidant Activity.

Taxus wallichiana Zucc., commonly known as the Himalayan Yew, is currently experiencing endangerment due to excessive harvesting and sluggish growth resulting from the extraction of paclitaxel, a crucial plant-derived medication employed in the treatment of cancer. T. wallichiana contains various phytochemicals, including paclitaxel, a diterpenoid that has been utilized as an anticancer medication. In order to extract paclitaxel while maintaining the species' survival, it is difficult to determine the most effective plant parts. We determined the diterpenoid paclitaxel content using modern analytical methods such as high-performance thin-layer chromatography-densitometric analysis. Furthermore, toxicological evaluations were carried out and tissue-specific antioxidant activity was statistically analyzed using 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS), ferric reducing antioxidant power (FRAP), Folin-Ciocâlteu (FC), and 2,2-diphenyl-ß-picrylhydrazyl (DPPH) assays. The results of our study offer significant contributions to the identification of optimal plant components for the extraction of paclitaxel. This information is crucial in the conservation of T. wallichiana and in mitigating the difficulties associated with its threatened classification. The present investigation makes a valuable contribution toward the advancement of sustainable methodologies in the manufacturing of paclitaxel, as well as the preservation of T. wallichiana for posterity. Bark exhibited the maximum paclitaxel yield at a content of 29162.3 µg/g dry weight. The accuracy of the method has been validated in accordance with the guidelines outlined by the International Council for Harmonisation (ICH). The current investigation evaluated the potential cytotoxic and genotoxic effects of the aqueous extracts on meristematic cells from the roots ofAllium cepa. The extracts obtained from the bark exhibited noteworthy cytotoxic and mitotic characteristics. The current investigation holds potential significance for the pharmaceutical sector in terms of identifying superior chemotypes of T. wallichiana that produce high levels of paclitaxel. Conducting a toxicological assessment on various tissues of T. wallichiana chemotypes through employment of the Allium cepa test would facilitate the identification of any potential genotoxic characteristics. The present study aimed to investigate four distinct assays, namely, DPPH, ABTS, FRAP, and FC, for the evaluation of the antioxidant potential of diverse T. wallichiana plant extracts and standard substances. The findings suggest that FRAP and ABTS exhibit a strong correlation. In general, the entirety of the tissue extract exhibited commendable antioxidant capacity, thereby rendering it a promising contender for diverse applications.

Ligand-based active targeting strategies for cancer theranostics.

In the past decades, for the intermediate or advanced cancerous stages, preclinical and clinical applications of nanomedicines in cancer theranostics have been extensively studied. Nevertheless, decreased specificity and poor targeting efficiency with low target concentration of theranostic are the major drawbacks of nanomedicine in employing clinical substitution over conventional systemic therapy. Consequently, ligand decorated nanocarrier-mediated targeted drug delivery system can transcend the obstructions through their enhanced retention activity and increased permeability with effective targeting. The highly efficient and specific nanocarrier-mediated ligand-based active therapy is one of the novel and promising approaches for delivery of the therapeutics for different cancers in recent years to restrict various cancer growth in vivo without harming healthy cells. The article encapsulates the features of nanocarrier-mediated ligands in augmentation of active targeting approaches of various cancers and summarizes ligand-based targeted delivery systems in treatment of cancer as plausible theranostics.

Mycoviral gene-incorporating phytopathogenic fungi: a biocontrol agent.

Fungal pathogens cause devastating agroeconomic losses. Chemical fungicides are used to control fungal diseases, although this is not an ecofriendly approach. A recent study by Liu et al. highlighted the use of mycoviral gene-incorporating phytopathogenic fungi as biocontrol agents for disease management.

Approaches for in vitro propagation and production of plumbagin in Plumbago spp.

The genus Plumbago (family Plumbaginaceae), commonly known as leadwort, is a sub-tropical shrub that produces secondary metabolite plumbagin, which is employed by pharmaceutical companies and in clinical research. Plumbagin is a potent pharmaceutical because of its anti-microbial, anti-malarial, antifungal, anti-inflammatory, anti-carcinogenic, anti-fertility, anti-plasmodium, antioxidant, anti-diabetic, and other effects. This review documents the biotechnological innovations used to produce plumbagin. The use of modern biotechnological techniques can lead to a variety of benefits, including better yield, increased extraction efficiency, mass production of plantlets, genetic stability, increased biomass, and more. Large-scale in vitro propagation is necessary to minimize over-exploitation of the natural population and allow the use of various biotechnological techniques to improve the plant species and secondary metabolite production. During in vitro culture, optimum conditions are requisites for explant inoculation and plant regeneration. In this review, we provide information on various aspects of plumbagin, depicting its structure, biosynthesis, and biotechnological aspects (both conventional and advanced) along with the future prospects. KEY POINTS: • Critical assessment on in vitro biotechnology in Plumbago species • In vitro propagation of Plumbago and elicitation of plumbagin • Biosynthesis and sustainable production of plumbagin.

Exploring the potential of CRISPR/Cas genome editing for vegetable crop improvement: An overview of challenges and approaches.

Vegetables provide many nutrients in the form of fiber, vitamins, and minerals, which make them an important part of our diet. Numerous biotic and abiotic stresses can affect crop growth, quality, and yield. Traditional and modern breeding strategies to improve plant traits are slow and resource intensive. Therefore, it is necessary to find new approaches for crop improvement. Clustered regularly interspaced short palindromic repeats/CRISPR associated 9 (CRISPR/Cas9) is a genome editing tool that can be used to modify targeted genes for desirable traits with greater efficiency and accuracy. By using CRISPR/Cas9 editing to precisely mutate key genes, it is possible to rapidly generate new germplasm resources for the promotion of important agronomic traits. This is made possible by the availability of whole genome sequencing data and information on the function of genes responsible for important traits. In addition, CRISPR/Cas9 systems have revolutionized agriculture, making genome editing more versatile. Currently, genome editing of vegetable crops is limited to a few vegetable varieties (tomato, sweet potato, potato, carrot, squash, eggplant, etc.) due to lack of regeneration protocols and sufficient genome sequencing data. In this article, we summarize recent studies on the application of CRISPR/Cas9 in improving vegetable trait development and the potential for future improvement.

Mangiferin: the miraculous xanthone with diverse pharmacological properties.

Mangiferin (1,3,6,7-tetrahydroxy-2-[3,4,5-trihydroxy-6-(hydroxymethyl) oxan-2-yl] xanthen-9-one) is a bioactive component derived primarily from the mango tree. Belonging to the Xanthone family, its structure allows it to engage with a variety of pharmacological targets. The symmetric linked core of xanthones has a heterogeneous biogenetic background. The carbon atoms are designated in a biochemical order, which reveals the reason of ring A (C1-C4) being referred to as acetate originated, and ring B (C5-C8) is referred to as shikimate originated. The antibacterial, hypocholesterolemic, antiallergic, cardiotonic, antidiabetic, anti-neoplastic, neuroprotective, antioxidant and immunomodulatory properties have all been demonstrated for the secondary metabolite. This study assessed and explained the important medical properties of mangiferin available in published literature, as well as its natural source, biosynthesis, absorption and bioavailability; multiple administration routes; metabolism; nanotechnology for enhanced efficacy of mangiferin and its toxicity, to aid the anticipated on-going potential of mangiferin as a novel diagnostic treatment.

Unravelling the pharmacological properties of cryptolepine and its derivatives: a mini-review insight.

Cryptolepine (1,5-methyl-10H-indolo[3,2-b]quinoline), an indoloquinoline alkaloid, found in the roots of Cryptolepis sanguinolenta (Lindl.) Schltr (family: Periplocaceae), is associated with the suppression of cancer and protozoal infections. Cryptolepine also exhibits anti-bacterial, anti-fungal, anti-hyperglycemic, antidiabetic, anti-inflammatory, anti-hypotensive, antipyretic, and antimuscarinic properties. This review of the latest research data can be exploited to create a basis for the discovery of new cryptolepine-based drugs and their analogues in the near future. PubMed, Scopus, and Google Scholar databases were searched to select and collect data from the existing literature on cryptolepine and their pharmacological properties. Several in vitro studies have demonstrated the potential of cryptolepine A as an anticancer and antimalarial molecule, which is achieved through inhibiting DNA synthesis and topoisomerase II. This review summarizes the recent developments of cryptolepine pharmacological properties and functional mechanisms, providing information for future research on this natural product.

Biotechnological and endophytic-mediated production of centellosides in Centella asiatica.

In vitro culture of a plant cell, tissue and organ is a marvellous, eco-friendly biotechnological strategy for the production of phytochemicals. With the emergence of recent biotechnological tools, genetic engineering is now widely practiced enhancing the quality and quantity of plant metabolites. Triterpenoid saponins especially asiaticoside and madecassoside of Centella asiatica (L.) Urb. are popularly known for their neuroprotective activity. It has become necessary to increase the production of asiaticoside and madecassoside because of their high pharmaceutical and industrial demand. Thus, the review aims to provide efficient biotechnological tools along with proper strategies. This review also included a comparative analysis of various carbon sources and biotic and abiotic elicitors. The vital roles of a variety of plant growth regulators and their combinations have also been evaluated at different in vitro growth stages of Centella asiatica. Selection of explants, direct and callus-mediated organogenesis, root organogenesis, somatic embryogenesis, synthetic seed production etc. are also highlighted in this study. In a nutshell, this review will present the research outcomes of different biotechnological interventions used to increase the yield of triterpenoid saponins in C. asiatica. KEY POINTS: • Critical and updated assessment on in vitro biotechnology in C. asiatica. • In vitro propagation of C. asiatica and elicitation of triterpenoid saponins production. • Methods for mass producing C. asiatica.

Naturally-Occurring Bioactives in Oral Cancer: Preclinical and Clinical Studies, Bottlenecks and Future Directions.

Oral cancer (OC) is the eighth most common cancer, particularly prevalent in developing countries. Current treatment includes a multidisciplinary approach, involving chemo, radio, and immunotherapy and surgery, which depends on cancer stage and location. As a result of the side effects of currently available drugs, there has been an increasing interest in the search for naturally-occurring bioactives for treating all types of cancer, including OC. Thus, this comprehensive review aims to give a holistic view on OC incidence and impact, while highlights the preclinical and clinical studies related to the use of medicinal plants for OC prevention and the recent developments in bioactive synthetic analogs towards OC management. Chemoprophylactic therapies connect the use of natural and/or synthetic molecules to suppress, inhibit or revert the transformation of oral epithelial dysplasia (DOK) into oral squamous cell carcinoma (OSCC). Novel searches have underlined the promising role of plant extracts and phytochemical compounds, such as curcumin, green tea extract, resveratrol, isothiocyanates, lycopene or genistein against this malignancy. However, poor bioavailability and lack of in vivo and clinical studies and complex pharmacokinetic profiles limit their huge potential of application. However, recent nanotechnological and related advances have shown to be promising in improving the bioavailability, absorption and efficacy of such compounds.

In vitro propagation and secondary metabolite production in Gloriosa superba L.

Gloriosa superba L., commonly known as "gloriosa lily," "glory lily," and "tiger claw," is a perennial climber in the Liliaceae family. This plant is used in African and Southeast Asian cultures as an ayurvedic medicinal herb to treat various health conditions. Its main bioactive component is colchicine, which is responsible for medicinal efficacies as well as poisonous properties of the plant. A high market demand, imprudent harvesting of G. superba from natural habitat, and low seed setting have led scientists to explore micropropagation techniques and in vitro optimization of its phytochemicals. Plant growth regulators have been used to induce callus, root, and shoot organogenesis, and somatic embryogenesis in vitro. This review is aimed at presenting information regarding the occurrence, taxonomic description, phytochemistry, micropropagation, in vitro secondary metabolite, and synthetic seed production. The data collected from the existing literature, along with an analysis of individual study details, outcomes, and variations in the reports, will contribute to the development of biotechnological strategies for conservation and mass propagation of G. superba. KEY POINTS: • Latest literature on micropropagation of Gloriosa superba. • Biotechnological production and optimization of colchicine. • Regeneration, somatic embryogenesis, and synthetic seed production.

Unravelling the multi-faceted regulatory role of polyamines in plant biotechnology, transgenics and secondary metabolomics.

Polyamines (PAs) are ubiquitous low-molecular-weight, aliphatic compounds with wide as well as complex application in fundamental areas of plant growth and development. PAs are mediator of basic metabolism of organisms which include cell division and differentiation, biotic and abiotic stress tolerance, reversal of oxidative damage, stabilization of nucleic acids, and protein and phospholipid binding. In plants, it attributes in direct and indirect organogenesis, endogenous phytohormone regulation, cellular compartmentalization, fruit and flower development, senescence, and secondary metabolite production which are highly tuned as first line of defense response. There are several aspects of polyamine-directed mechanism that regulate overall plant growth in vitro and in vivo. In the present review, we have critically discussed the role played by polyamine on the enhanced production of bioactive natural products and how the same polyamines are functioning against different environmental stress conditions, i.e., salinity, drought, high CO2 content, herbivory, and physical wounding. The role of polyamines on elicitation process has been highlighted previously, but it is important to note that its activity as growth regulator under in vitro condition is correlated with an array of intertwined mechanism and physiological tuning. Medicinal plants under different developmental stages of micropropagation are characterized with different functional aspects and regulatory changes during embryogenesis and organogenesis. The effect of precursor molecules as well as additives and biosynthetic inhibitors of polyamines in rhizogenesis, callogenesis, tuberization, embryogenesis, callus formation, and metabolite production has been discussed thoroughly. The beneficial effect of exogenous application of PAs in elicitation of secondary metabolite production, plant growth and morphogenesis and overall stress tolerance are summarized in this present work. KEY POINTS: • Polyamines (PAs) play crucial roles in in vitro organogenesis. • PAs elicitate bioactive secondary metabolites (SMs). • Transgenic studies elucidate and optimize PA biosynthetic genes coding SMs.

Therapeutic strategies to overcome taxane resistance in cancer.

One of the primary causes of attenuated or loss of efficacy of cancer chemotherapy is the emergence of multidrug resistance (MDR). Numerous studies have been published regarding potential approaches to reverse resistance to taxanes, including paclitaxel (PTX) and docetaxel, which represent one of the most important classes of anticancer drugs. Since 1984, following the FDA approval of paclitaxel for the treatment of advanced ovarian carcinoma, taxanes have been extensively used as drugs that target tumor microtubules. Taxanes, have been shown to affect an array of oncogenic signaling pathways and have potent cytotoxic efficacy. However, the clinical success of these drugs has been restricted by the emergence of cancer cell resistance, primarily caused by the overexpression of MDR efflux transporters or by microtubule alterations. In vitro and in vivo studies indicate that the mechanisms underlying the resistance to PTX and docetaxel are primarily due to alterations in α-tubulin and ß-tubulin. Moreover, resistance to PTX and docetaxel results from: 1) alterations in microtubule-protein interactions, including microtubule-associated protein 4, stathmin, centriole, cilia, spindle-associated protein, and kinesins; 2) alterations in the expression and activity of multidrug efflux transporters of the ABC superfamily including P-glycoprotein (P-gp/ABCB1); 3) overexpression of anti-apoptotic proteins or inhibition of apoptotic proteins and tumor-suppressor proteins, as well as 4) modulation of signal transduction pathways associated with the activity of several cytokines, chemokines and transcription factors. In this review, we discuss the abovementioned molecular mechanisms and their role in mediating cancer chemoresistance to PTX and docetaxel. We provide a detailed analysis of both in vitro and in vivo experimental data and describe the application of these findings to therapeutic practice. The current review also discusses the efficacy of different pharmacological modulations to achieve reversal of PTX resistance. The therapeutic roles of several novel compounds, as well as herbal formulations, are also discussed. Among them, many structural derivatives had efficacy against the MDR phenotype by either suppressing MDR or increasing the cytotoxic efficacy compared to the parental drugs, or both. Natural products functioning as MDR chemosensitizers offer novel treatment strategies in patients with chemoresistant cancers by attenuating MDR and increasing chemotherapy efficacy. We broadly discuss the roles of inhibitors of P-gp and other efflux pumps, in the reversal of PTX and docetaxel resistance in cancer cells and the significance of using a nanomedicine delivery system in this context. Thus, a better understanding of the molecular mechanisms mediating the reversal of drug resistance, combined with drug efficacy and the application of target-based inhibition or specific drug delivery, could signal a new era in modern medicine that would limit the pathological consequences of MDR in cancer patients.