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Background Obesity is among the most serious public health problems worldwide, with few safe pharmaceutical interventions. Natural products have become an important source of potential anti-obesity therapeutics. Dihydromyricetin (DHM) exerts antidiabetic effects. The biochemical target of DHM, however, has been unknown. It is crucial to identify the biochemical target of DHM for elucidating its physiological function and therapeutic value. Objectives The objective of this study was to identify the biochemical target of DHM. Methods An abundant antiadipogenic flavanonol was extracted from the herbal plant Ampelopsis grossedentata through bioassay-guided fractionation and characterized with high-resolution LC-MS and 1H and 13C nuclear magnetic resonance. Antiadipogenic experiments were done with mouse 3T3-L1 preadipocytes. A biochemical target of the chemical of interest was identified with drug affinity responsive target stability assay. Direct interactions between the chemical of interest and the protein target in vitro were predicted with molecular docking and subsequently confirmed with surface plasmon resonance. Expression levels of peroxisome proliferator-activated receptor γ (PPARγ), which is associated with 78-kDa glucose-regulated protein (GRP78), were measured with real-time qPCR. Results DHM was isolated, purified, and structurally characterized. Cellular studies showed that DHM notably reduced intracellular oil droplet formation in 3T3-L1 cells with a median effective concentration of 294 μM (i.e., 94 μg/mL). DHM targeted the ATP binding site of GRP78, which is associated with adipogenesis. An equilibrium dissociation constant between DHM and GRP78 was 21.8 μM. In 3T3-L1 cells upon treatment with DHM at 50 μM (i.e., 16 μg/mL), the expression level of PPARγ was downregulated to 53.9% of the solvent vehicle control's level. Conclusions DHM targets GRP78 in vitro. DHM is able to reduce lipid droplet formation in 3T3-L1 cells through a mode of action that is plausibly associated with direct interactions between GRP78 and DHM, which is a step forward in determining potential applications of DHM as an anti-obesity agent.

Sugarcane smut, caused by Sporisorium scitamineum, is one of the most devastating fungal diseases affecting sugarcane worldwide. To develop a potent sugarcane smut fungicide, secondary metabolites of marine-derived Bacillus siamensis were isolated and screened for inhibitory activities, which led to the discovery of five new 24-membered macrolactins, bamemacrolactins A-E (1-5), with 3 being the most potent inhibitor. The antifungal mechanism of 3 was studied by assessing its effects on mycelial morphology and the cell wall. Differential proteomics were used to analyze proteins in S. scitamineum upon treatment with bamemacrolactin C and to elucidate its antifungal mechanism. A total of 533 differentially expressed proteins were found. After the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, eight target proteins were selected, and their functions were discussed. Six of the eight proteins were reported as antifungal targets. The target proteins are involved in the oxidative phosphorylation pathway. Therefore, the potent inhibition of S. scitamineum by compound 3 is most likely through oxidative phosphorylation and targeting a series of enzymes.

Glucose-regulated protein 78 (GRP78), a molecular chaperone, is overexpressed in patients suffering from obesity, fatty liver, hyperlipidemia and diabetes. GRP78, therefore, can be not only a biomarker to predict the progression and prognosis of obesity and metabolic diseases but also a potential therapeutic target for anti-obesity treatment. In this paper, GRP78 inhibitors targeting its ATPase domain have been reviewed. Small molecules and proteins that directly bind GRP78 have been described. Putative mechanisms of GRP78 in regulating lipid metabolism were also summarized so as to investigate the role of GRP78 in obesity and other related diseases and provide a theoretical basis for the development and design of anti-obesity drugs targeting GRP78.

Sugarcane smut, caused by

The R2R3-MYB family is one of the largest plant transcription factor (TF) families playing vital roles in defense, plant growth, and secondary metabolism biosynthesis. Although this gene family has been studied in many species, isoflavonoid biosynthesis-related R2R3-MYB TFs in Callerya speciosa (Champ. ex Benth.) Schot, a traditional Chinese medicinal herb, are poorly understood. Here, a total of 101 R2R3-MYB TFs were identified from C. speciosa transcriptome dataset. 25 clades divided into five functional groups were clustered based on the sequence similarity and phylogenetic tree. Conserved motifs and domain distribution, expression patterns, and coexpression networks were also employed to identify the potential R2R3-MYB TFs in the regulation of isoflavonoid biosynthesis. In silico evaluation showed that the deduced R2R3-CsMYB proteins contain highly conserved R2R3 repeat domain at the N-terminal region, that is the signature motif of R2R3-type MYB TFs. Eight potential TFs (CsMYB17, CsMYB36, CsMYB41, CsMYB44, CsMYB45, CsMYB46, CsMYB72, and CsMYB81) had high degrees of coexpression with four key isoflavonoid biosynthetic genes (CsIFS, CsCHS7, CsHID-1, and CsCHI3), in which CsMYB36 as a potential regulator possessed the highest degree. HPLC analysis showed that formononetin and maackiain contents were significantly increased during the development of tuberous roots, which might be controlled by both related R2R3-CsMYBs and structural genes involved in the isoflavonoid biosynthesis pathway. The transcriptome data were further validated by reverse transcription real-time PCR (RT-qPCR) analysis, and similar expression profiles between TFs and key structural genes were identified. This study was the first step toward the understanding of the R2R3-MYB TFs regulating isoflavonoid biosynthesis in C. speciosa. The results will provide information for further functional analysis and quality improvement through genetic manipulation of these potential R2R3-CsMYB genes in C. speciosa.

Industrial hemp (Cannabis sativa L.) is a fast-growing and high biomass producing plant species with wide usage of its materials such as fiber, food, and fuel. There are many varieties containing low concentration of tetrahydrocannabinol (THC). In the present study, it assessed the agricultural feasibility of three industrial hemp varieties with different water management and nitrogen fertilizer treatments, and determined the best ones to cultivate in Hawaii, then evaluated the effects of plant density on the yield and the potential phytoremediation for the herbicide atrazine. The field experiments indicated that it was difficult to grow the variety F75 in Hawaii with a final weight of 13 g and did not live for the full growth season. However, the subtropical fiber hemp variety CHG grew to height of about 190 cm and its weight varied from 150 g to 280 g between two planting densities (100 plants m−2 and 28 plants m−2, respectively). The subtropical seed hemp variety CHY was intermediate at a mean height and weight of about 130 cm and 130 g, respectively. Estimated crop yields were 19 tons acre-1 year-1 (dry weight) for CHG stalks that could be used for building construction and 16 tons acre-1 year-1 (dry weight) for leaves could be used as animal forage. Approximately, 1.7 tons of seeds could be harvested per acre per year from variety CHY. Little water consumption (10 mm week-1) was needed, which corresponds with drought resistance of CHG variety. Use of nitrogen fertilizer at a rate of 100 kg ha-1 did not improve growth of CHG variety more than the existing nitrogen levels in the soil. Phytoremediation potential of industrial hemp was also assessed by field pot studies, in which field soils were fortified with 0, 0.25 and 0.50 mg kg-1 of atrazine. The half-life (t1/2) of atrazine in hemp watered pots was 15 days, whereas t1/2 was approximately 50 and 28 days in the no plant non-watered pots and the no plant watered pots, respectively, suggesting the degradation of atrazine in soils showed a higher efficiency planted with hemp under water irrigation condition. The CHG plants accumulated atrazine from soils, and the enrichment factor in CHG was increased over the course of 28 days (from 0.22 %–0.31 % to 0.63 %–0.89 %), then decreased after 49 days (0.28 %–0.30 %). Overall, these findings revealed that industrial hemp plants were useful for phytoremediation of soils contaminated with atrazine.

Halosulfuron-methyl (HSM) is a safe, selective and effective sulfonylurea herbicide (SU) for the control of sedge and broadleaf weeds in sugarcane, corn, tomato, and other crops. The primary site of action is acetolactate synthase (ALS), a key enzyme of branched chain amino acids (BCAAs) synthesis. In addition to ALS inhibition, BCAAs deficiencies and oxidative damage may be involved in toxic effects of SUs. However, secondary targets of HSM relevant to plant physiological responses are unclear. In the present study, comparative growth inhibition and peroxidization injury between sensitive and tolerance crops were observed at biochemical and physiological levels suggesting involvement of H 2 O 2 , ethylene, salicylic acid (SA) in the oxidative stress responses to HSM. HSM caused accumulation of H 2 O 2 , stimulated photorespiration and consequent accumulation of SA that worsened the peroxidization injury to the sensitive C 3 plant soybean ( Glycine max). The growth inhibition at low concentrations of HSM could be lessened by supplementary BCAAs, reactive oxygen species scavengers or ethylene inducers, whereas the oxidation damage at high concentrations of HSM could not be reversed and ultimately lead to plant death. H 2 O 2 at a low level stimulated the antioxidase system including glutathione S-transferase activities in the HSM-tolerant C 4 maize ( Zea mays ), which contributes to HSM tolerance. H 2 O 2 plays an important role on HSM stress responses in both HSM-sensitive and HSM-tolerant soybean and maize.

Halosulfuron-methyl (HSM) is a safe, selective and effective sulfonylurea herbicide (SU) for the control of sedge and broadleaf weeds in sugarcane, corn, tomato, and other crops. The primary site of action is acetolactate synthase (ALS), a key enzyme of branched chain amino acids (BCAAs) synthesis. In addition to ALS inhibition, BCAAs deficiencies and oxidative damage may be involved in toxic effects of SUs. However, secondary targets of HSM relevant to plant physiological responses are unclear. In the present study, comparative growth inhibition and peroxidization injury between sensitive and tolerance crops were observed at biochemical and physiological levels suggesting involvement of H