A reference-grade genome assembly for Gossypium bickii and insights into its genome evolution and formation of pigment glands and gossypol.

The pigment gland is a morphological characteristic of Gossypium and its related genera. Gossypium bickii (G1) is characterized by delayed pigment gland morphogenesis in the cotyledons. In this study, a reference-grade genome of G1 was generated, and comparative genomics analysis showed that G1 was closest to Gossypium australe (G2), followed by A- and D-genome species. Two large fragment translocations in chromosomes 5 and 13 were detected between the G genome and other Gossypium genomes and were unique to the G1 and G2 genomes. Compared with the G2 genome, two large fragment inversions in chromosomes 12 and 13 were detected in G1. According to the phylogeny, divergence time, and similarity analysis of nuclear and chloroplast genomes, G1 was formed by hybridization between Gossypium sturtianum (C1) and a common ancestor of G2 and Gossypium nelsonii (G3). The coordinated expression patterns of pigment gland formation (GoPGF) and gossypol biosynthesis genes in G1 were verified to be consistent with its phenotype, and nine genes that were related to the process of pigment gland formation were identified. A novel gene, GbiCYP76B6, regulated by GoPGF, was found to affect gossypol biosynthesis. These findings offer insights into the origin and evolution of G1 and its mechanism of pigment gland formation and gossypol biosynthesis.

Hepatoprotective Potential of Pomegranate in Curbing the Incidence of Acute Liver Injury by Alleviating Oxidative Stress and Inflammatory Response.

Hepatitis is an inflammatory disease of the liver and is considered one of the leading causes of death worldwide. Due to its scavenging activity, Punica granatum may be used for the treatment and prevention of liver diseases. The current study investigated the protective mechanism underlying the effects of pomegranate against a rat model of carbon tetrachloride-induced liver injury. Intraperitoneal injection of CCl4 resulted in liver inflammation, oxidative stress, and accumulation of lipid in hepatocytes. CCl4 induced a downregulation of superoxide dismutase (SOD), glutathione (GSH), and melonaldehyde (MDA). Pomegranate protection was assessed in terms of biochemical parameters, histopathology, and immunohistochemistry. Promegranate administration decreased inflammation, elevated serum enzymes and ROS production, and countered the debilitating effects caused by CCl4. In addition, CCl4-induced histological changes were absent in the crude pomegranate extract group, which also enhanced the scavenging activity of reactive oxygen species by enhancing the antioxidant defense mechanism as confirmed by detecting MDA, SOD, and GSH expressions. The migration of CD68+ macrophages was halted at the injured area of the central vein and the number of macrophages was reduced to the normal control by the crude extract compared to the positive control silymarin group. Likewise, protective effects of ethylacetate and the aqueous fraction of the crude extract were also observed. However, the butanol and n-hexane fractions displayed increased levels of ALT, AST, and ALP as compared to silymarin. About 25% damage to hepatocytes was observed in the butanol and n-hexane group by histopathological examination, which is a little better compared to the CCl4-treated group. The crude extract and its ethyl acetate and aqueous fractions may be accountable for the hepatoprotective potential of Punica granatum, which was further confirmed by in vivo experiments. Together, these findings confirm that pomegranate exerts hepatoprotective activity against CCl4-induced oxidative stress and liver damage.

Govaniadine Ameliorates Oxidative Stress, Inflammation, and Kupffer Cell Activation in Carbon Tetrachloride-Induced Hepatotoxicity in Rats.

Liver diseases such as hepatic carcinoma are one of the main health problems worldwide. Herbal drugs are largely used to treat liver injury in the indigenous system of medicine and may provide lead compounds for hepatoprotective drug discovery. The present study is investigated to test the Corydalis govaniana Wall. extract, fraction, and isolate therapeutically active constituents to explore their hepatoprotective, anti-inflammatory, and antioxidant activities. For this purpose, the antioxidant activity of govaniadine, caseadine, caseamine, and protopine was performed by assessing the scavenging events of the stable 2,2-diphenyl-1-picrylhydrazyl. Hepatoprotection of govaniadine was assessed in terms of reduction in serum enzymes (alanine aminotransferase, aspartate transaminase, and alkaline phosphatase) caused by CCl4-induced liver injury in rats and by histopathological techniques. All the compounds showed significant antioxidant activity with a percentage inhibition of 92.2, 86.7, 85.3, and 79.7, respectively, compared to propyl gallate 90.3%. Treatment with govaniadine reduced the serum enzyme level down to normal levels in the CCl4-treated group while inhibiting the increase of malondialdehyde, and the induction of superoxide dismutase and the glutathione level was upregulated. Histopathology showed ∼47% damage to the liver cells in the CCl4-treated group; reduction in this damaged area was found to be better upon using govaniadine. Immunohistochemistry results showed that govaniadine as compared to silymarin has exceedingly decreased the inflammation by halting the CCl4-induced activation of hepatic macrophages. In carrageenan-induced paw edema assay, govaniadine significantly alleviated the edema after 1-5 h at a dose of 20 mg/kg (26.00 and 28.5%), 50 mg/kg (22.05 and 27.0%), and 100 mg/kg (20.02 and 25.30%), respectively. The results of our experiments suggest that govaniadine showed antioxidant and hepatoprotective activity in liver injury. The hepatoprotective function of govaniadine may be associated to the scavenging of the free radical and attenuation of oxidative stress as well as inflammatory responses in the liver. Hence, govaniadine may be a lead compound for the hepatoprotective drug discovery process and further research is needed to find out their molecular mechanism of protection.

Physiological, ultrastructural, biochemical, and molecular responses of glandless cotton to hexavalent chromium (Cr6+) exposure.

Glandless cotton can be grown to obtain cotton seeds free of toxic gossypol for use as both food and feed. However, they are not grown normally due to their lesser productivity and higher susceptibility to biotic stress. Great attention has been paid to biotic stresses rather than abiotic stresses on glandless cotton. Chromium (Cr) is a common pollutant of soil and considered a serious threat to plants due to its adverse effects on different functions. Although numerous studies are available on the toxicity of Cr6+ in various plants. However, its adverse effects and mechanism of toxicity in glandless cotton can seldom be found in the literature. This study examined the Cr6+ effect on glandless cotton in comparison to glanded cotton. Four pairs of glanded and glandless cotton near-isogenic lines (NILs) were exposed to different doses (0, 10, 50, and 100 µM/L) of Cr6+ for seven days, and biochemical, physiological, molecular, and ultrastructure changes were observed, which were significantly affected by Cr6+ at high concentrations in all NILs. The effect of Cr6+ on ionic contents shows the same trend in glanded and glandless NILs except for manganese (Mn2+) that show inhibition in glandless (ZMS-12w and Coker-312w) and enhance in the glanded NIL (ZMS-17). The gene expression of superoxide dismutase (SOD) and peroxidase (POD) revealed similar trends as enzyme activities in glandless NILs. The principal component analysis (PCA) and Agglomerative hierarchical clustering (AHC) results of all NILs from morpho-physiological traits, cluster ZMS-16, and ZMS-17 into Cr6+ sensitive group. While the glandless NILs have the potential to cope with the Cr toxicity by increasing the antioxidant enzyme activity and their gene expression. This study also revealed that Cr6+ tolerance in cotton is genotypic and has an independent mechanism in the root that not related to low gossypol.

Reduced Glutathione Protects Subcellular Compartments From Pb-Induced ROS Injury in Leaves and Roots of Upland Cotton (Gossypium hirsutum L.).

Heavy metals-based changes in the plants and their alleviation through eco-friendly agents including reduced glutathione (GSH) have been widely studied. In the present experiment, we tested the alleviatory role of reduced glutathione (GSH) in seedlings of upland cotton cultivar, TM-1 under lead (Pb) toxicity. Plants were grown in the Hoagland solution containing Pb (0 µM), Pb (500 µM), GSH (50 µM), and GSH + Pb (50 µM + 500 µM). Lead exposure exacerbated hydrogen peroxide (H2O2) and hydroxyl radical (OH•) levels, induced lipid peroxidation (MDA), and decreased the activities of catalase (CAT) and ascorbate peroxidase (APX) in the terminal and median leaves of 28-days old cotton seedlings stressed for 10 days. However, in the primary and secondary roots, CAT activity was increased but APX decreased. Similarly, peroxidase (POD) and superoxide dismutase (SOD) activities were enhanced in the median leaves but a declining trend was observed in the terminal leaves, primary roots and secondary roots. Glutathione reductase (GR) activity, ascorbic acid (AsA) contents and GSH concentrations were increased in all parts except AsA in the median leaves. Transmission electron micrographs of Pb-treated plants exhibited deformed cell wall and cell membrane, disfigured chloroplasts and irregularly shaped mitochondria in the terminal and median leaves. Further, cell membrane, mitochondria, nucleus and other cell organelles in root cells were severely affected by the Pb. Thus their identification was little bit difficult through ultramicroscopy. External GSH stabilized leaf and root ultramorphology by stabilizing cell membranes, stimulating formation of multivesicular body vesicles, and by maintaining structural integrity of other organelles. Evidently, GSH played major alleviatory role against Pb toxicity in upland cotton.

Steroidal alkaloids efficient aromatase inhibitors with potential for the treatment of postmenopausal breast cancer.

Plant-derived natural products are of great interest due to their diversity in modern drug discovery. Sarcococca saligna has been used for the treatment of different diseases. The present study was aimed at isolating phytochemical constituents including Alkaloid-C (a), Dictyophlebine (b), Sarcovagine-D (c) and Saracodine (d) Holaphylline (e) from Sarcococca saligna to investigate the anticancer effect of these compounds. These compounds were evaluated for inhibition of aromatase enzyme of breast cancer in assistance by molecular docking simulations to understand molecular interaction between the enzyme and ligands. The IC50 values of compound 1 and 5 were found 138.27 ± 0.01 µl and 12.91 ± 0.01 µl, respectively, and both were found active due to their bulky structures in comparison to the active site of aromatase enzyme. The standard drug exemestane showed potent activity in comparison with the test compounds, having IC50 values of 0.052 ± 0.01 µl. Both compounds showed favorable electrostatic interactions with the active site of aromatase enzyme but the shape and steric bulk of the compounds was the limiting factor in their inhibitory effects. New lead compounds could be generated after extensive modifications guided by computational and experimental tools as a possible anticancer agents by targeting aromatase enzyme.