Anti-Adipogenic Activity of High-Phenolic Sorghum Brans in Pre-Adipocytes.

Obesity is one of the leading public health problems that can result in life-threatening metabolic and chronic diseases such as cardiovascular diseases, diabetes, and cancer. Sorghum (Sorghum bicolor (L.) Moench) is the fifth most important cereal crop in the world and certain genotypes of sorghum have high polyphenol content. PI570481, SC84, and commercially available sumac sorghum are high-polyphenol genotypes that have demonstrated strong anti-cancer activities in previous studies. The objective of this study was to explore a potential anti-obesity use of extracts from sorghum bran in the differentiation of 3T3-L1 preadipocytes and to investigate cellular and molecular responses in differentiated adipocytes to elucidate related mechanisms. None of the four different sorghum bran extracts (PI570481, SC84, Sumac, and white sorghum as a low-polyphenol control) caused cytotoxicity in undifferentiated and differentiated 3T3-L1 cells at doses used in this study. Sorghum bran extracts (PI570481, SC84, and Sumac) reduced intracellular lipid accumulation and expression of adipogenic and lipogenic proteins in a dose-dependent manner in differentiated 3T3-L1 cells. The same polyphenol containing sorghum bran extracts also repressed production of reactive oxygen species (ROS) and MAPK signaling pathways and repressed insulin signaling and glucose uptake in differentiated 3T3-L1 cells. These data propose a potential use of high-phenolic sorghum bran for the prevention of obesity.

Polyphenol Containing Sorghum Brans Exhibit an Anti-Cancer Effect in Apc Min/+ Mice Treated with Dextran Sodium Sulfate.

Colon cancer (CC) is considered a high-risk cancer in developed countries. Its etiology is correlated with a high consumption of red meat and low consumption of plant-based foods, including whole grains. Sorghum bran is rich in polyphenols. This study aimed to determine whether different high-phenolic sorghum brans suppress tumor formation in a genetic CC rodent model and elucidate mechanisms. Tissue culture experiments used colorectal cancer cell lines SW480, HCT-116 and Caco-2 and measured protein expression, and protein activity. The animal model used in this study was APC Min+/mouse model combined with dextram sodium sulfate. High phenolic sorghum bran extract treatment resulted in the inhibition of proliferation and induced apoptosis in CC cell lines. Treatment with high phenolic sorghum bran extracts repressed TNF-α-stimulated NF-κB transactivation and IGF-1-stimulated PI3K/AKT pathway via the downregulation of ß-catenin transactivation. Furthermore, high-phenolic sorghum bran extracts activated AMPK and autophagy. Feeding with high-phenolic sorghum bran for 6 weeks significantly suppressed tumor formation in an APC Min/+ dextran sodium sulfate promoted CC mouse model. Our data demonstrates the potential application of high-phenolic sorghum bran as a functional food for the prevention of CC.

Anticancer Activity of a Novel High Phenolic Sorghum Bran in Human Colon Cancer Cells.

Human colon cancer is the third leading cause of mortality in the United States and worldwide. Chemoprevention using diet is widely accepted as a promising approach for cancer management. Numerous population studies indicate a negative correlation between the incidence of colon cancer and consumption of whole grains with a high content of bioactive phenolic compounds. In the current study, we evaluated the anticancer properties of a high phenolic sorghum bran extract prepared using 70% ethanol with 5% citric acid solvent at room temperature. A significant dose-dependent suppression of cell proliferation was observed in human colon cancer cells treated with the high phenolic sorghum bran extract. Apoptosis and S phase growth arrest were induced, while cell migration and invasion were inhibited by this treatment; these effects were accompanied by altered expression of apoptosis, cell cycle, and metastasis-regulating genes. We also found that the high phenolic sorghum bran extract stimulated DNA damage in association with induction of extracellular signal-regulated kinase (ERK) and c-Jun-NH2-terminal kinase (JNK) and subsequent expression of activating transcription factor 3 (ATF3). The present study expands our understanding of the potential use of high phenolic sorghum bran to prevent human colon cancer.

High-polyphenol extracts from Sorghum bicolor attenuate replication of Legionella pneumophila within RAW 264.7 macrophages.

Polyphenols derived from a variety of plants have demonstrated antimicrobial activity against diverse microbial pathogens. Legionella pneumophila is an intracellular bacterial pathogen that opportunistically causes a severe inflammatory pneumonia in humans, called Legionnaires' Disease, via replication within macrophages. Previous studies demonstrated that tea polyphenols attenuate L. pneumophila intracellular replication within mouse macrophages via increased tumor necrosis factor (TNF) production. Sorghum bicolor is a sustainable cereal crop that thrives in arid environments and is well-suited to continued production in warming climates. Sorghum polyphenols have anticancer and antioxidant properties, but their antimicrobial activity has not been evaluated. Here, we investigated the impact of sorghum polyphenols on L. pneumophila intracellular replication within RAW 264.7 mouse macrophages. Sorghum high-polyphenol extract (HPE) attenuated L. pneumophila intracellular replication in a dose-dependent manner but did not impair either bacterial replication in rich media or macrophage viability. Moreover, HPE treatment enhanced both TNF and IL-6 secretion from L. pneumophila infected macrophages. Thus, polyphenols derived from sorghum enhance macrophage restriction of L. pneumophila, likely via increased pro-inflammatory cytokine production. This work reveals commonalities between plant polyphenol-mediated antimicrobial activity and provides a foundation for future evaluation of sorghum as an antimicrobial agent.

Deterioration of ovary plays a key role in heat stress-induced spikelet sterility in sorghum.

In sorghum (Sorghum bicolor [L.] Moench), the impact of heat stress during flowering on seed set is known, but mechanisms that lead to tolerance are not known. A diverse set of sorghum genotypes was tested under controlled environment and field conditions to ascertain the impact of heat stress on time-of-day of flowering, pollen viability, and ovarian tissue. A highly conserved early morning flowering was observed, wherein >90% of spikelets completed flowering within 30 min after dawn, both in inbreds and hybrids. A strong quantitative impact of heat stress was recorded before pollination (reduced pollen viability) and post pollination (reduced pollen tube growth and linear decline in fertility). Although viable pollen tube did reach the micropylar region, 100% spikelet sterility was recorded under 40/22°C (day/night temperatures), even in the tolerant genotype Macia. Heat stress induced significant damage to the ovarian tissue near the micropylar region, leading to highly condensed cytoplasmic contents and disintegrated nucleolus and nucleus in the susceptible genotype RTx430. Whereas, relatively less damages to ovarian cell organelles were observed in the tolerant genotype Macia under heat stress. Integrating higher tolerance in female reproductive organ will help in effective utilization of the early morning flowering mechanism to enhance sorghum productivity under current and future hotter climate.

High-Polyphenol Sorghum Bran Extract Inhibits Cancer Cell Growth Through ROS Induction, Cell Cycle Arrest, and Apoptosis.

As diet is one of the major controllable factors in cancer development, potentially chemopreventive foods are of significant interest to public health. One such food is sorghum (Sorghum bicolor), a cereal grain that contains varying concentrations of polyphenols. In a panel of 15 sorghum germplasm, we identified strains with higher polyphenol content than previously reported for this grain. Bran extracts from the germplasm with the highest and lowest polyphenol content were then tested against HepG2 and Caco2 cancer cells to assess effects on cancer cell viability, reactive oxygen species, apoptosis, DNA damage, cell cycle arrest, and protein expression patterns. High-polyphenol extracts, but not low-polyphenol extracts, reduced cell viability by inducing apoptosis and cell cycle arrest following production of reactive oxygen species and oxidative DNA damage. The results indicate that high-polyphenol sorghum bran extracts have potential anticancer properties and warrant further research, not only to test against specific cancers but also to elucidate underlying mechanisms of action.