Corrigendum to 'Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics' [Genes & Diseases 10 (2023) 1367-1401].

[This corrects the article DOI: 10.1016/j.gendis.2022.02.007.].

Corrigendum: Phytotherapy for attention deficit hyperactivity disorder (ADHD): a systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fphar.2022.827411.].

Tissue-specific variations of piperine in ten populations of Piper longum L.: bioactivities and toxicological profile.

P. longum L., one of the most significant species of the genus Piperaceae, is most frequently employed in Indian-Ayurvedic and other traditional medicinal-systems for treating a variety of illnesses. The alkaloid piperine, is the key phytoconstituent of the plant, primarily responsible for its' pharmacological-impacts. The aim of the study is to analyse the intra-specific variation in piperine content among different chemotypes (PL1 to PL 30) and identify high piperine yielding chemotype (elite-chemotype) collected from 10 different geographical regions of West Bengal by validated HPTLC chromatography method. The study also focused on the pharmacological-screening to better understand the antioxidant activity of the methanol extracts of P. longum by DPPH and ABTS radical-scavenging activity and genotoxic activity by Allium cepa root tip assay. It was found that the P. longum fruit chemotypes contain high amount piperine (highest 16.362 mg/g in chemotype PL9) than the stem and leaf chemotypes. Both DPPH and ABTS antioxidant assays revealed that P. longum showed moderate radical-scavenging activity and the highest activity was found in PL9 (fruit) chemotype with IC50 values of 124.2 ± 0.97 and 104 ± 0.78 µg/ml respectively. The A. cepa root tip assay showed no such significant genotoxic-effect and change in mitotic-index. The quick, reproducible, and validated HPTLC approach offers a useful tool for determining quantitative variations of piperine among P. longum chemotypes from different geographical-regions and also according to the different tissues and choose elite genotypes with high piperine production for continued propagation and commercialization for the pharmaceutical sector. Additionally, the plant's in-vitro antioxidant property and lack of genotoxicity directly supports its' widespread and long history of use as a medicinal and culinary plant.

Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics.

Cancer is an abnormal state of cells where they undergo uncontrolled proliferation and produce aggressive malignancies that causes millions of deaths every year. With the new understanding of the molecular mechanism(s) of disease progression, our knowledge about the disease is snowballing, leading to the evolution of many new therapeutic regimes and their successive trials. In the past few decades, various combinations of therapies have been proposed and are presently employed in the treatment of diverse cancers. Targeted drug therapy, immunotherapy, and personalized medicines are now largely being employed, which were not common a few years back. The field of cancer discoveries and therapeutics are evolving fast as cancer type-specific biomarkers are progressively being identified and several types of cancers are nowadays undergoing systematic therapies, extending patients' disease-free survival thereafter. Although growing evidence shows that a systematic and targeted approach could be the future of cancer medicine, chemotherapy remains a largely opted therapeutic option despite its known side effects on the patient's physical and psychological health. Chemotherapeutic agents/pharmaceuticals served a great purpose over the past few decades and have remained the frontline choice for advanced-stage malignancies where surgery and/or radiation therapy cannot be prescribed due to specific reasons. The present report succinctly reviews the existing and contemporary advancements in chemotherapy and assesses the status of the enrolled drugs/pharmaceuticals; it also comprehensively discusses the emerging role of specific/targeted therapeutic strategies that are presently being employed to achieve better clinical success/survival rate in cancer patients.

Biotechnology of Passiflora edulis: role of Agrobacterium and endophytic microbes.

Two forms of the genus Passiflora, belonging to the Passifloraceae family, are commonly called yellow and purple passion. These perennial woody climbers are found in the cooler regions at higher altitudes and in lowlands of tropical areas. The presence of alkaloids, terpenes, stilbenes, flavonoids, glycosides, carotenoids, etc. in different parts of the plant provides several pharmacological properties. Because of the various uses in foods and pharmaceuticals, in vitro propagation of this genus has been performed hugely and is of great interest to researchers. From different explants via direct organogenesis under controlled aseptic conditions, callus, root, shoot, and somatic embryos are induced successfully. Different PGRs are augmented in the media for the rapid multiplication or organogenesis, especially, the high ratio of cytokinin and auxin in the basal media efficiently regenerates the shoot and root respectively. The in vitro regenerated plantlets are then acclimatized and hardened properly before transferring to the field conditions. Thus, the present first of its kind review on P. edulis exclusively encompasses the wide applications of biotechnology for this species alongside its organogenesis, embryogenesis, cytology, and endophytic microbes with special emphasis on the role of genetic transformation studies mediated by Agrobacterium sp. KEY POINTS: • Critical assessment on in vitro biotechnology in P. edulis. • Agrobacterium-mediated transformation in P. edulis. • Role of endophytic microbes in P. edulis.

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.

Biotechnological interventions and production of galanthamine in Crinum spp.

Genus Crinum L. is a member of the Amaryllidaceae family having beautiful, huge, ornamental plants with umbels of lily-like blooms that are found in tropical and subtropical climates all over the world. For thousands of years, Crinum has been used as a traditional medicine to treat illnesses and disorders. Numerous distinct alkaloids of the Amaryllidaceae group, whose most well-known properties include analgesic, anticholinergic, antitumor, and antiviral, have recently been discovered by phytochemical analyses. However, because of decades of overexploitation for their economically significant bioactive ingredients and poor seed viability and germination rates, these plants are now threatened in their native environments. Because of these factors, researchers are investigating micropropagation techniques to optimize phytochemicals in vitro. This review's objective is to offer details on the distribution, phytochemistry, micropropagation, in vitro galanthamine synthesis, and pharmacology which will help to design biotechnological techniques for the preservation, widespread multiplication, and required secondary metabolite production from Crinum spp. KEY POINTS: • Botanical description and phytochemical profile of Crinum spp. • In vitro micropropagation method of Crinum sp. • Bioactive compound galanthamine isolation techniques and its pharmacological properties.

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.

Piper longum L.: A comprehensive review on traditional uses, phytochemistry, pharmacology, and health-promoting activities.

Piper longum (family Piperaceae), commonly known as "long-pepper" or "Pippali" grows as a perennial shrub or as an herbaceous vine. It is native to the Indo-Malaya region and widely distributed in the tropical and subtropical world including the Indian subcontinent, Sri Lanka, Middle-East, and America. The fruits are mostly used as culinary spice and preservatives and are also a potent remedy in various traditional medicinal systems against bronchitis, cough, cold, snakebite, and scorpion-sting and are also used as a contraceptive. Various bioactive-phytochemicals including alkaloids, flavonoids, esters, and steroids were identified from the plant extracts and essential oils from the roots and fruits were reported as antimicrobial, antiparasitic, anthelminthic, mosquito-larvicidal, antiinflammatory, analgesic, antioxidant, anticancer, neuro-pharmacological, antihyperglycaemic, hepato-protective, antihyperlipidaemic, antiangiogenic, immunomodulatory, antiarthritic, antiulcer, antiasthmatic, cardioprotective, and anti-snake-venom agents. Many of its pharmacological properties were attributed to its antioxidative and antiinflammatory effects and its ability to modulate a number of signalling pathways and enzymes. This review comprehensively encompasses information on habit, distribution, ethnobotany, phytochemistry, and pharmacology of P. longum in relation to its medicinal importance and health benefits to validate the traditional claims supported by specific scientific experiments. In addition, it also discusses the safety and toxicity studies, application of green synthesis and nanotechnology as well as clinical trials performed with the plant also elucidating research gaps and future perspectives of its multifaceted uses.

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.

Biotechnological interventions and indole alkaloid production in Rauvolfia serpentina.

Rauvolfia serpentina (L). Benth. ex Kurz. (Apocynaceae), commonly known as Sarpagandha or Indian snakeroot, has long been used in the traditional treatment of snakebites, hypertension, and mental illness. The plant is known to produce an array of indole alkaloids such as reserpine, ajmaline, amalicine, etc. which show immense pharmacological and biomedical significance. However, owing to its poor seed viability, lesser germination rate and overexploitation for several decades for its commercially important bioactive constituents, the plant has become endangered in its natural habitat. The present review comprehensively encompasses the various biotechnological tools employed in this endangered Ayurvedic plant for its in vitro propagation, role of plant growth regulators and additives in direct and indirect regeneration, somatic embryogenesis and synthetic seed production, secondary metabolite production in vitro, and assessment of clonal fidelity using molecular markers and genetic transformation. In addition, elicitation and other methods of optimization of its indole-alkaloids are also described herewith. KEY POINTS: • Latest literature on in vitro propagation of Rauvolfia serpentina • Biotechnological production and optimization of indole alkaloids • Clonal fidelity and transgenic studies in R. serpentina.

Betelvine (Piper betle L.): A comprehensive insight into its ethnopharmacology, phytochemistry, and pharmacological, biomedical and therapeutic attributes.

Piper betle L. (synonym: Piper betel Blanco), or betel vine, an economically and medicinally important cash crop, belongs to the family Piperaceae, often known as the green gold. The plant can be found all over the world and is cultivatedprimarily in South East Asian countries for its beautiful glossy heart-shaped leaves, which are chewed or consumed as betelquidand widely used in Chinese and Indian folk medicine, as carminative, stimulant,astringent, against parasitic worms, conjunctivitis, rheumatism, wound, etc., andis also used for religious purposes. Hydroxychavicol is the most important bioactive compound among the wide range of phytoconstituents found in essential oil and extracts. The pharmacological attributes of P. betle are antiproliferation, anticancer, neuropharmacological, analgesic, antioxidant, antiulcerogenic, hepatoprotective, antifertility, antibacterial, antifungal and many more. Immense attention has been paid to nanoformulations and their applications. The application of P. betle did not show cytotoxicity in preclinical experiments, suggesting that it could serve as a promising therapeutic candidate for different diseases. The present review comprehensively summarizes the botanical description, geographical distribution, economic value and cultivation, ethnobotanical uses, preclinical pharmacological properties with insights of toxicological, clinical efficacy, and safety of P. betle. The findings suggest that P. betle represents an orally active and safe natural agent that exhibits great therapeutic potential for managing various human medical conditions. However, further research is needed to elucidate its underlying molecular mechanisms of action, clinical aspects, structure-activity relationships, bioavailability and synergistic interactions with other drugs.

Biotechnology for micropropagation and camptothecin production in Ophiorrhiza sp.

Camptothecin (CPT) is a monoterpenoid-alkaloid, an anticancer compound from plant. Ever since its discovery in 1996 from the bark of Camptotheca acuminata, various researches have been conducted for enhancing its production. CPT has also been reported in several other species belonging to the plant families Icacinaceae, Rubiaceae, Apocynaceae, Nyssaceae, Betulaceae, Violaceae, Meliaceae, and Gelseminaceae. Out of these, Ophiorrhiza sp. (Rubiaceae) is the next possible candidate for sustainable CPT production after C. acuminata and Nothapodytes nimoonia. Various biotechnological-studies have been conducted on Ophiorrhiza sp. for searching the elite species and the most optimal strategies for CPT production. The genus Ophiorrhiza has been used as medicines for antiviral, antifungal, antimalarial, and anticancer activities. Phytochemical analysis has revealed the presence of alkaloids, flavonoids, triterpenes, and CPT from the plant. Because of the presence of CPT and its herbaceous habit, Ophiorrhiza sp. has now become a hot topic in research area. Currently, for mass production of the elite spp., tissue culture techniques have been implemented. In the past decades, several researchers have contributed on the diversity assessment, phytochemical analysis, mass production, and in vitro production of CPT in Ophiorrhiza sp. In this paper, we review the on the biotechnological strategies, optimal culture medium, micropropagation of Ophiorrhiza sp., effect of PGR on shoot formation, rhizogenesis, callus formation, and enhanced production of CPT for commercial use. KEY POINTS: • Latest literature on in vitro propagation of Ophiorrhiza sp. • Biotechnological production of camptothecin and related compounds • Optimization, elicitation, and transgenic studies in Ophiorrhiza sp.

Phytotherapy for Attention Deficit Hyperactivity Disorder (ADHD): A Systematic Review and Meta-analysis.

Attention deficit hyperactivity disorder (ADHD) is commonly a neurodevelopmental behavioural disorder in children and adolescents. Mainly characterized by symptoms like lack of attention, hyperactivity, and impulsiveness, it can impact the overall mental development of the one affected. Several factors, both genetic and non-genetic, can be responsible for this disorder. Although several traditional treatment methods involve medication and other counselling techniques, they also come with different side effects. Hence, the choice is now shifting to alternative treatment techniques. Herbal treatments are considered one of the most popular complementary and alternative medicine (CAM) administered. However, issues related to the safety and efficacy of herbal remedies for the treatment of ADHD need to be investigated further. This study aims to find out the recent advancement in evidence-based use of herbal remedies for ADHD by a comprehensive and systematic review that depicts the results of the published works on herbal therapy for the disorder. The electronic databases and the references retrieved from the included studies present related randomized controlled trials (RCTs) and open-label studies. Seven RCTs involving children and adolescents diagnosed with ADHD met the inclusion criteria. There is a fair indication of the efficacy and safety of Melissa officinalis L., Bacopa monnieri (L.) Wettst., Matricaria chamomilla L., and Valeriana officinalis L. from the studies evaluated in this systematic review for the treatment of various symptoms of ADHD. Limited evidence was found for Ginkgo biloba L. and pine bark extract. However, various other preparations from other plants did not show significant efficacy. There is inadequate proof to strongly support and recommend the administration of herbal medicines for ADHD, but more research is needed in the relevant field to popularize the alternative treatment approach.

Biotechnology for propagation and secondary metabolite production in Bacopa monnieri.

Bacopa monnieri (L.) Wettst. or water hyssop commonly known as "Brahmi" is a small, creeping, succulent herb from the Plantaginaceae family. It is popularly employed in Ayurvedic medicine as a nerve tonic to improve memory and cognition. Of late, this plant has been reported extensively for its pharmacologically active phyto-constituents. The main phytochemicals are brahmine, alkaloids, herpestine, and saponins. The saponins include bacoside A, bacoside B, and betulic acid. Investigation into the pharmacological effect of this plant has thrived lately, encouraging its neuroprotective and memory supporting capacity among others. Besides, it possesses many other therapeutic activities like antimicrobial, antioxidant, anti-inflammatory, gastroprotective properties, etc. Because of its multipurpose therapeutic potential, it is overexploited owing to the prioritization of natural remedies over conventional ones, which compels us to conserve them. B. monnieri is confronting the danger of extinction from its natural habitat as it is a major cultivated medico-botanical and seed propagation is restricted due to less seed availability and viability. The ever-increasing demand for the plant can be dealt with mass propagation through plant tissue culture strategy. Micropropagation utilizing axillary meristems as well as de novo organogenesis have been widely investigated in this plant which has also been explored for its conservation and production of different types of secondary metabolites. Diverse in vitro methods such as organogenesis, cell suspension, and callus cultures have been accounted for with the aim of production and/or enhancement of bacosides. Direct shoot-organogenesis was initiated in excised leaf and internodal explants without any exogenous plant growth regulator(s) (PGRs), and the induction rate was improved when exogenous cytokinins and other supplements were used. Moreover, biotechnological toolkits like Agrobacterium-mediated transformation and the use of mutagens have been reported. Besides, the molecular marker-based studies demonstrated the clonal fidelity among the natural and in vitro generated plantlets also elucidating the inherent diversity among the natural populations. Agrobacterium-mediated transformation system was mostly employed to optimize bacoside biosynthesis and heterologous expression of other genes. The present review aims at depicting the recent research outcomes of in vitro studies performed on B. monnieri which include root and shoot organogenesis, callus induction, somatic embryogenesis, production of secondary metabolites by in vitro propagation, acclimatization of the in vitro raised plantlets, genetic transformation, and molecular marker-based studies of clonal fidelity. KEY POINTS: • Critical and up to date records on in vitro propagation of Bacopa monnieri • In vitro propagation and elicitation of secondary metabolites from B. monnieri • Molecular markers and transgenic studies in B. monnieri.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated genome-editing toolkit to enhance salt stress tolerance in rice and wheat.

The rice and wheat agricultural system is the primary source of food for billions across the world. However, the productivity and long-term sustainability of rice and wheat are threatened by a large number of abiotic stresses, especially salinity stress. Salinity has a significant impact on plant development and productivity and is one of the leading causes of crop yield losses in agricultural soils worldwide. Over the last few decades, several attempts have been undertaken to enhance salinity stress tolerance, most of which have relied on traditional or molecular breeding approaches. These approaches have so far been insufficient in addressing the issues of abiotic stress. However, due to the availability of genome sequences for cereal crops like rice and wheat and the development of genome editing techniques like clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein9 (Cas9), it is now possible to "edit" genes and influence key traits. Here, we review the application of the CRISPR/Cas9 system in both rice (Oryza sativa L.) and wheat (Triticum aestivum L.) to develop salinity tolerant cultivars. The CRISPR/Cas genome editing toolkit holds great promise of producing cereal crops tolerant to salt stress to increase agriculture resilience with a strong impact on the environment and public health.

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.

Unraveling the promise and limitations of CRISPR/Cas system in natural product research: Approaches and challenges.

An incredible array of natural products is produced by plants that serve several ecological functions, including protecting them from herbivores and microbes, attracting pollinators, and dispersing seeds. In addition to their obvious medical applications, natural products serve as flavoring agents, fragrances, and many other uses by humans. With the increasing demand for natural products and the development of various gene engineering systems, researchers are trying to modify the plant genome to increase the biosynthetic pathway of the compound of interest or blocking the pathway of unwanted compound synthesis. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 has had widespread success in genome editing due to the system's high efficiency, ease of use, and accuracy which revolutionized the genome editing system in living organisms. This study highlights the method of the CRISPR/Cas system, its application in different organisms including microbes, algae, fungi, and also higher plants in natural product research, and its shortcomings and future prospects.

Biotechnological interventions of in vitro propagation and production of valuable secondary metabolites in Stevia rebaudiana.

Plant cell and tissue culture makes provision of a sustainable and nature-friendly strategy for the production of secondary metabolites, and modern progress in gene editing and genome engineering provides novel possibilities to improve both the qualitative and quantitative aspects of such phytochemicals. The ever-expanding quest for plant-based medicine to treat diabetes facilitates large-scale cultivation of Stevia rebaudiana to enhance the yield of its much-coveted low-calorie sweetener glycosides. The potential to process stevia as a "natural" product should enhance the acceptance of steviosides as a natural calorie-free sweetener especially suitable for use in diabetic and weight control drinks and foods. Besides sweetener agents, S. rebaudiana is a potent source of many antioxidant compounds and is used to cure immunodeficiencies, neurologic disorders, inflammation, diabetes mellitus, Parkinson's disease, and Alzheimer's disease. This comprehensive review presents the research outcomes of the many biotechnological interventions implicated to upscale the yield of steviol glycosides and its derivatives in in vitro cell, callus, tissue, and organ cultures with notes on the use of bioreactor and genetic engineering in relation to the production of these valuable compounds in S. rebaudiana. KEY POINTS: • Critical and updated assessment on sustainable production of steviol glycosides from Stevia rebaudiana. • In vitro propagation of S. rebaudiana and elicitation of steviol glycosides production. • Genetic fidelity and diversity assessment of S. rebaudiana using molecular markers.

Optimization of harvest and extraction factors by full factorial design for the improved yield of C-glucosyl xanthone mangiferin from Swertia chirata.

Swertia chirata Buch.-Ham. ex C.B. Clarke is an important medicinal plant used in various herbal formulations as it shows significant biological activities such as hepatoprotective, hypoglycemic, anti-inflammatory, antimalarial, antioxidant and anti-parkinson. C-glucosyl xanthone glycoside (mangiferin) is known as bio-marker compound of genus Swertia L. Development of efficient extraction methods of C-glucosyl xanthone mangiferin from Swertia chirata was attempted by optimizing the pre-harvest, post-harvest and extraction techniques by full factorial design. Firstly, a full factorial design was implemented to evaluate the single and interactive effects of pre-harvest (growth stage and plant part), post-harvest (drying condition and storage periods) followed by selection of best extraction technique such as heat reflux extraction (HRE), microwave assisted extraction (MAE) and ultrasound assistant extraction (UAE) at different solvent types on mangiferin yield. HPTLC and HPLC techniques were used for the determination of mangiferin content in extracts generated from different plant samples. In addition, anti-oxidant and anti-diabetic properties were determined by using DPPH assay and percentage inhibition of α­amylase enzyme. Substantial variation of mangiferin yield, ranged from 1.46 to 4.86% was observed, depending on the growth stage, plant part, drying condition, storage periods and extraction method. Results showed that drying of the leaves of Swertia chirata in the shade harvested at budding stage and stored for not more than 1 month was recommended for obtaining a higher mangiferin yield. Among different extraction techniques, MAE and UAE in 50% aqueous ethanol solvent were found to be efficient and cost-effective with better yield of mangiferin (4.82% and 4.86%, respectively) as compared to HRE (4.14%). Highest DPPH activity and percentage inhibition of α­amylase was observed in the aqueous ethanol extract of S. chirata leaves harvested at bud-stage of plant followed by flowering stage. The study shows that optimization of various factors by full factorial design was found to be an effective procedure to improve mangiferin yield from Swertia chirata and can be used for extraction of mangiferin.