Guggulsterone - a potent bioactive phytosteroid: synthesis, structural modification, and its improved bioactivities.

Guggulsterone is a phytosteroid derived from the oleo-gum resin of the critically endangered plant Commiphora wightii. This molecule has attracted increasing attention due to its excellent biochemistry potential and the compound has consequently been evaluated in clinical trials. With a low concentration in natural resources but wide medicinal and therapeutic value, chemists have developed several synthetic routes for guggulsterone starting from various steroid precursors. Moreover, numerous studies have attempted to modify its structure to improve the biological properties. Nowadays, green and sustainable chemistry has also attracted more attention for advanced chemical processes and reactions in steroid chemistry. The present review aimed to summarize the literature and provide an update about the improvements in the chemical synthesis and structural modification of guggulsterone from the view of green chemistry. Moreover, this review encompasses the improved activities of structurally modified guggulsterone derivatives. We expect that the information provided here will be useful to researchers working in this field and on this molecule.

Significance and genetic control of membrane transporters to improve phytoremediation and biofortification processes.

Humans frequently consume plant-based foods in their daily life. Contamination of agricultural soils by heavy metals (HMs) is a major food and nutritional security issue. The crop plants grown in HM-contaminated agricultural soil may accumulate more HMs in their edible part, further transferring into the food chain. Consumption of HM-rich crops can cause severe health issues in humans. On the other hand, the low content of the essential HM in the edible part of the crop also causes health problems. Therefore, researchers must try to reduce the non-essential HM in the edible part of the crop plants and improve the essential HMs. Phytoremediation and biofortification are the two strategies for resolving this problem. The genetic component helps to improve the efficiency of phytoremediation and biofortification processes in plants. They help eliminate HMs from soil and improve essential HM content in crop plants. The membrane transporter genes (genetic components) are critical in these two strategies. Therefore, engineering membrane transporter genes may help reduce the non-essential HM content in the edible part of crop plants. Targeted gene editing by genome editing tools like CRISPR could help plants achieve efficient phytoremediation and biofortification. This article covers gene editing's scope, application, and implication to improve the phytoremediation and biofortification processes in non-crop and crop plants.

Improvement of millets in the post-genomic era.

Millets are food and nutrient security crops in the semi-arid tropics of developing countries. Crop improvement using modern tools is one of the priority areas of research in millets. The whole-genome sequence (WGS) of millets provides new insight into understanding and studying the genes, genome organization and genomic-assisted improvement of millets. The WGS of millets helps to carry out genome-wide comparison and co-linearity studies among millets and other cereal crops. This approach might lead to the identification of genes underlying biotic and abiotic stress tolerance in millets. The available genome sequence of millets can be used for SNP identification, allele discovery, association and linkage mapping, identification of valuable candidate genes, and marker-assisted breeding (MAB) programs. Next generation sequencing (NGS) technology provides opportunities for genome-assisted breeding (GAB) through genomic selection (GS) and genome-wide association studies (GAWS) for crop improvement. Clustered, regularly interspaced, short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) genome editing (GE) system provides new opportunities for millet improvement. In this review, we discuss the details on the WGS available for millets and highlight the importance of utilizing such resources in the post-genomic era for millet improvement. We also draw inroads on the utilization of various approaches such as GS, GWAS, functional genomics, gene validation and GE for millet improvement. This review might be helpful for understanding the developments in the post-genomic era of millet improvement.

Insights to improve the plant nutrient transport by CRISPR/Cas system.

We need to improve food production to feed the ever growing world population especially in a changing climate. Nutrient deficiency in soils is one of the primary bottlenecks affecting the crop production both in developed and developing countries. Farmers are forced to apply synthetic fertilizers to improve the crop production to meet the demand. Understanding the mechanism of nutrient transport is helpful to improve the nutrient-use efficiency of crops and promote the sustainable agriculture. Many transporters involved in the acquisition, export and redistribution of nutrients in plants are characterized. In these studies, heterologous systems like yeast and Xenopus were most frequently used to study the transport function of plant nutrient transporters. CRIPSR/Cas system introduced recently has taken central stage for efficient genome editing in diverse organisms including plants. In this review, we discuss the key nutrient transporters involved in the acquisition and redistribution of nutrients from soil. We draw insights on the possible application CRISPR/Cas system for improving the nutrient transport in plants by engineering key residues of nutrient transporters, transcriptional regulation of nutrient transport signals, engineering motifs in promoters and transcription factors. CRISPR-based engineering of plant nutrient transport not only helps to study the process in native plants with conserved regulatory system but also aid to develop non-transgenic crops with better nutrient use-efficiency. This will reduce the application of synthetic fertilizers and promote the sustainable agriculture strengthening the food and nutrient security.

Structure, Function, Regulation and Phylogenetic Relationship of ZIP Family Transporters of Plants.

Zinc (Zn) is an essential micronutrient for plants and humans. Nearly 50% of the agriculture soils of world are Zn-deficient. The low availability of Zn reduces the yield and quality of the crops. The zinc-regulated, iron-regulated transporter-like proteins (ZIP) family and iron-regulated transporters (IRTs) are involved in cellular uptake of Zn, its intracellular trafficking and detoxification in plants. In addition to Zn, ZIP family transporters also transport other divalent metal cations (such as Cd2+, Fe2+, and Cu2+). ZIP transporters play a crucial role in biofortification of grains with Zn. Only a very limited information is available on structural features and mechanism of Zn transport of plant ZIP family transporters. In this article, we present a detailed account on structure, function, regulations and phylogenetic relationships of plant ZIP transporters. We give an insight to structure of plant ZIPs through homology modeling and multiple sequence alignment with Bordetella bronchiseptica ZIP (BbZIP) protein whose crystal structure has been solved recently. We also provide details on ZIP transporter genes identified and characterized in rice and other plants till date. Functional characterization of plant ZIP transporters will help for the better crop yield and human health in future.

Hepatoprotective effect of bisbenzylisoquinoline alkaloid tiliamosine from Tiliacora racemosa in high-fat diet/diethylnitrosamine-induced non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is one of the aggressive forms of non-alcoholic fatty liver disease (NAFLD) and is a potential risk factor of HCC. This study reports the curative effect of tiliamosine on NASH. Tiliamosine was isolated from Tiliacora racemosa Colebr. (Menispermaceae) and its structure was confirmed by studying the physical and spectroscopic data. The effects of tiliamsoine on lipid accumulation and lipotoxicity were evaluated using palmitate-oleate induced steatosis in HepG2 cells. The in vivo efficacy of tiliamosine was evaluated using HFD fed, DEN induced non-alcoholic steatohepatitis Wistar rats. In HepG2 cells, tiliamosine did not affect the cell viability up to 100 µM concentration and showed GI25 value of 264.28 µM. The treatment with tiliamsoine significantly lowered the ORO concentration by 44.17% and triglyceride accumulation by 69.32% at 50 µM concentration (P < 0.005). It also reduced the leakage of LDH and transaminases in PO-BSA induced HepG2 cells. The treatment with tiliamsoine significantly decreased the plasma levels of transaminases, phosphatase and LDH (P < 0.05) in HFD-DEN induced steatohepatitis. The histology and the immunohistochemistry of the hepatic sections were in accordance with the biochemical findings. Preliminary molecular analysis indicated that the hepatic FXR expression was upregulated and TNFα expression was downregulated by the treatment with tiliamsoine. This study provided preliminary evidence on the use of tiliamosine for the treatment of NASH.

Curative effect of arjunolic acid from Terminalia arjuna in non-alcoholic fatty liver disease models.

The prevalence of Non Alcoholic Fatty Liver Disease (NAFLD) is increasing globally. Terminalia arjuna W. & Arn. (Combretaceae) is an endemic tree found in India and Sri Lanka and used traditionally for its cardioprotective and hepatoprotective effects. Arjunolic acid (AA) is an oleanane triterpenoid found mainly in the heartwood of T. arjuna. This study was aimed to evaluate the hepatoprotective effect of AA using cellular and rodent models of NAFLD. AA was isolated from the ethyl acetate extract of the heartwood of T. arjuna. The structure of AA was confirmed by physical and spectroscopic data. Steatosis was induced in HepG2 cells using palmitate-oleate mixture and the effects of AA on triglyceride accumulation and lipotoxicity were assessed. In vivo effect of AA on NAFLD was assessed using HFD fed rats. The treatment with AA did not affect the cell viability upto 100 µM and showed GI25 value of 379.9 µM in HepG2 cells. The treatment with AA significantly lowered the ORO concentration by 35.98% and triglyceride accumulation by 66.36% at 50 µM concentration (P < 0.005) compared to the vehicle treated group. The treatment with AA also reduced the leakage of ALT and AST by 61.11 and 48.29% in a significant manner (P < 0.005). The in vivo findings clearly demonstrated that the animals treated with AA at 25 and 50 mg/kg concentrations showed a significant decrease in the levels of transaminases, phosphatase and GGT (P < 0.005). In the liver, the expression of PPARα and FXRα expressions were upregulated, while PPARγ expression was downregulated by the treatment with AA. The liver histology of the animals showed reduction in steatosis and MNC infiltration. These preliminary evidences suggested that AA might be a promising lead to treat NAFLD. Future robust scientific studies on AA will lead to tailoring it for the treatment of NAFLD.

Finger Millet [Eleusine coracana (L.) Gaertn.] Improvement: Current Status and Future Interventions of Whole Genome Sequence.

The whole genome sequence (WGS) of the much awaited, nutrient rich and climate resilient crop, finger millet (Eleusine coracana (L.) Gaertn.) has been released recently. While possessing superior mineral nutrients and excellent shelf life as compared to other major cereals, multiploidy nature of the genome and relatively small plantation acreage in less developed countries hampered the genome sequencing of finger millet, disposing it as one of the lastly sequenced genomes in cereals. The genomic information available for this crop is very little when compared to other major cereals like rice, maize and barley. As a result, only a limited number of genetic and genomic studies has been undertaken for the improvement of this crop. Finger millet is known especially for its superior calcium content, but the high-throughput studies are yet to be performed to understand the mechanisms behind calcium transport and grain filling. The WGS of finger millet is expected to help to understand this and other important molecular mechanisms in finger millet, which may be harnessed for the nutrient fortification of other cereals. In this review, we discuss various efforts made so far on the improvement of finger millet including genetic improvement, transcriptome analysis, mapping of quantitative trait loci (QTLs) for traits, etc. We also discuss the pitfalls of modern genetic studies and provide insights for accelerating the finger millet improvement with the interventions of WGS in near future. Advanced genetic and genomic studies aided by WGS may help to improve the finger millet, which will be helpful to strengthen the nutritional security in addition to food security in the developing countries of Asia and Africa.

Identification of putative QTLs for seedling stage phosphorus starvation response in finger millet (Eleusine coracana L. Gaertn.) by association mapping and cross species synteny analysis.

A germplasm assembly of 128 finger millet genotypes from 18 countries was evaluated for seedling-stage phosphorus (P) responses by growing them in P sufficient (Psuf) and P deficient (Pdef) treatments. Majority of the genotypes showed adaptive responses to low P condition. Based on phenotype behaviour using the best linear unbiased predictors for each trait, genotypes were classified into, P responsive, low P tolerant and P non-responsive types. Based on the overall phenotype performance under Pdef, 10 genotypes were identified as low P tolerants. The low P tolerant genotypes were characterised by increased shoot and root length and increased root hair induction with longer root hairs under Pdef, than under Psuf. Association mapping of P response traits using mixed linear models revealed four quantitative trait loci (QTLs). Two QTLs (qLRDW.1 and qLRDW.2) for low P response affecting root dry weight explained over 10% phenotypic variation. In silico synteny analysis across grass genomes for these QTLs identified putative candidate genes such as Ser-Thr kinase and transcription factors such as WRKY and basic helix-loop-helix (bHLH). The QTLs for response under Psuf were mapped for traits such as shoot dry weight (qHSDW.1) and root length (qHRL.1). Putative associations of these QTLs over the syntenous regions on the grass genomes revealed proximity to cytochrome P450, phosphate transporter and pectin methylesterase inhibitor (PMEI) genes. This is the first report of the extent of phenotypic variability for P response in finger millet genotypes during seedling-stage, along with the QTLs and putative candidate genes associated with P starvation tolerance.