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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2017 · IF 3.154

Metabolic Characterization of Dairy Cows Treated with Gossypol by Blood Biochemistry and Body Fluid Untargeted Metabolome Analyses

Chaohua Tang,Kai Zhang,Tengfei Zhan,Qingyu Zhao,Junmin Zhang

To characterize the metabolic disorders of dairy cows treated with gossypol, 12 dairy cows were assigned to either a control group or a treatment group that was fed 1000 mg of gossypol per kilogram of dry matter feed for 28 days. Milk quality was adversely affected, as both milk protein and lactose levels were significantly decreased in the gossypol-treated group (3.40% vs 3.16%, P = 0.044; 5.15% vs 4.91%, P = 0.027; respectively). Plasma samples revealed increases in alanine aminotransferase (P = 0.092), choline esterase (P = 0.02), and glutathione transferase (P = 0.0005) and decreases in glucose (P = 0.076) in the gossypol-treated group. Mass spectrometry based comparative metabolomic analyses showed reduced concentrations of the gluconeogenesis precursor l-glutamine (P = 0.047), with significant decreases (P < 0.05) in plasma l-lysine, l-threonine, and homoserine levels after gossypol treatment. HDL-C and LDL-C levels in the gossypol-treated group were increased (P = 0.044) and decreased (P = 0.023), respectively. These results demonstrate that gossypol induced oxidative stress and hepatotoxicity; reduced peripheral lipid metabolism, and enhanced hepatic lipid accumulation; decreased amino acid bioavailability and milk protein synthesis; and decreased gluconeogenesis and milk lactose in dairy cows.

研究领域: 动物营养学 · 代谢组学 · 兽医学
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INDUSTRIAL CROPS AND PRODUCTS · 2025 · IF 6.2

High foliar adhesion carvacrol-chitosan nanoparticles assist cotton against Fusarium oxysporum infection

Jing Zhou,Rourou Wang,Ming Niu,Zhenghua Zhang,Minrui Zhu,Lumei Pu,Weibing Xu,Runtian Ma

The infection caused by Fusarium oxysporum severely threatens cotton production. Herein, carvacrol-chitosan nanoparticles (CS@CAR) are facilely fabricated using tripolyphosphate as a crosslinker. When the initial mass ratio of chitosan to carvacrol is 1:0.4, the nanoparticles show the best stability and drug loading. Morphological analysis reveals that the CS@CAR nanoparticles possesses a uniform spherical structure with an average diameter of approximately 150 nm. About 51.23 % of total CAR is released within the 48 h in the simulated fungal infection environment. The contact angle of drug-loaded particles decreases by 12.2 and 6.6 ° compares with that of pure water and unloaded particles. The fluorescence intensity of leaves before and after rain erosion is 1.3 times and 1.2 times that of the pure water control group by fluorescence imaging analysis. The bacteriostatic activity of drug-loaded nanoparticles is 6–7 times that of non-drug-loaded nanoparticles. The contents of nucleic acid, protein, and malondialdehyde leaked by spores after treatment with drug-loaded particles are 1.4, 1.5 and 2.3 times those in the non-drug-loaded particle treatment group, respectively. The CS@CAR entirely prevents Fusarium oxysporum from infecting cotton leaves in spore inoculation experiments. The CS@CAR nanoparticles are expected to be used to prevent and control the infection of Fusarium oxysporum on cotton.

CAS / MDL: 499-75-2 9012-76-4
研究领域: 植物病理学 · 纳米生物学
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SAUDI PHARMACEUTICAL JOURNAL · 2021 · IF 4.33

Gastric floating tablet improves the bioavailability and reduces the hypokalemia effect of gossypol in vivo

Hao Liu,Sijiao Wang,Houyin Shi,Ruirui Zhang,Kunyan Qu,Yue Hu,Xingyu Qu,Chenyun Gan,Jingjing Chen,Xinyu Shi,Mengwu Zhang,Weiling Zeng

Gossypol (Gos) is a natural polyphenolic compound that has shown a number of valuable biological properties such as antifertility, antioxidation, and antitumor activities. However, the clinical application of Gos has been hindered by its notable adverse effects such as hypokalemia, hemolytic anemia, and so on. Using sustained-release dosage form provides a hopeful solution to this problem. In this study, a gastric floating tablet for sustained-release of Gos (Gos-GFT) was developed using polyvinylpyrrolidone, hydroxypropyl methyl cellulose, ethyl cellulose, lactose, sodium bicarbonate, and magnesium stearate. Gos-GFT had an average weight of around 200 mg with a drug content percentage of around 13.66%. The physicochemical properties of Gos-GFT satisfied the pharmacopoeial requirements for tablets. Gos-GFT was able to float in an acidic medium and had a sustained drug release for over 12 h. In vivo studies showed that the relative bioavailability of Gos-GFT, as compared with Gos powders, was larger than that of a non-gastric floating tablet which was a dosage form used for comparison with Gos-GFT. Furthermore, compared with the Gos powders and the non-gastric floating Gos tablets, Gos-GFT could prolong the in vivo action time of Gos, and significantly relieve hypokalemia which is a major adverse effect of Gos. These properties made Gos-GFT a promising Gos preparation that warrants further investigation for more extensive clinical applications of this natural compound.

研究领域: 药剂学 · 药物代谢动力学 · 毒理学
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EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY · 2015 ·Vol. 118 ·期 4 ·584-591 · IF 1.812

Free fatty acids increase gossypol losses in soybean oil during heating

Xiuhang Chai,Yanlan Bi,Shangde Sun

Gossypol is a highly reactive compound present in cotton plant ( Gossypium spp.). With the increase of heating temperature and time, gossypol losses increased significantly. In this work, the effect of free fatty acid (FFA) and peroxide value (PV) of soybean oil (SBO) on gossypol losses during heating was systematically studied. Results showed that the higher the content of FFAs of SBO at 120 or 180°C, the greater the gossypol losses. The HPLC and LC/MS analysis suggested that the increase of gossypol losses in SBO was due to the transformation of gossypol in the presence of FFAs at 120 or 180°C. The PV also had an observable effect on gossypol losses at 120 or 180°C, which was ascribed to be the transformation or oxidation of gossypol with hydroperoxides. Practical applications: Due to the toxicity of gossypol, the use of cottonseed oil and cottonseed meal is restricted. It is significantly meaningful to remove gossypol. The primary objective of this study was to investigate the effect of heating temperature and oil quality (AV and PV of oil) on gossypol losses in SBO during heating. More information about the changes of gossypol in oil was achieved, which could be used to guide the processing of cottonseed oil and cottonseed meal. At the same time, the mechanism of gossypol changes could be used to get high quality gossypol. The losses of gossypol in SBO were primarily due to the increasing transformation of gossypol under heating system. Gossypol was non-volatile and the higher the AV and PV of SBO, the more loss of the gossypol.

CAS / MDL: 112-80-1
研究领域: 食品科学 · 植物化学
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Journal of Zhejiang University-SCIENCE B · 2018 · IF 1.815

Pharmacokinetic comparison of gossypol isomers in cattle: transfer from diet to plasma and degradation by rumen microbes

Chao-hua Tang,Jia Liu,Qing-yu Zhao,Jun-min Zhang

A pharmacokinetic comparison of gossypol isomers in cattle was made by investigating their transfer from ingested food to plasma and their degradation by rumen microbes. The gossypol isomers in whole cottonseed, plasma, and rumen fluid were determined by high-performance liquid chromatography (HPLC). The intakes of (+)-and (−)-gossypol by cows on three farms were about 5.6–8.5 and 3.8–5.9 g/(d·herd), respectively. The plasma gossypol concentrations increased as ingestion increased and ranged from 0.31 to 0.48 μg/ml for the (+) form and from 0.39 to 0.59 μg/ml for the (−) form. The (+) form was slightly predominant (58.8%–59.8%) in the gossypol ingested by the cows, whereas the (−) form predominated (54.6%–55.9%) in the plasma. An in vitro study showed that at 6 h, 67.4% and 85.7% of the (−)-gossypol were degraded in 500 and 1000 μg/g treatment groups, respectively, and these increased to 83.6% and 92.5%, respectively, at 12 h. The regularity of the degradation of (+)-gossypol was similar to that of (−)-gossypol. These results showed that (−)-gossypol may be more persistent than (+)-gossypol in plasma, and that the degradation of the gossypol isomers in the rumen is rapid and not enantioselective in cattle.

CAS / MDL: 35320-23-1
研究领域: 动物科学 · 药理学
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AQUACULTURE NUTRITION · 2022 · IF 3.781

Lipotoxic Effects of Gossypol Acetate Supplementation on Hepatopancreas Fat Accumulation and Fatty Acid Profile in Cyprinus carpio

Yuru Zhang,Junmei Zhang,Yanhua Ren,Mengdan Zhang,Junping Liang

Cottonseed meal is an excellent protein source with low price and abundant nutrients, but the existence of free gossypol restricts its wide application in animal feeds. To explore the toxic effects of free gossypol, the effects of gossypol acetate on the growth performance, hepatopancreatic fat accumulation, and muscle fatty acid composition of the common carp (Cyprinus carpio) were investigated in the present study. Carp were randomly divided into four groups, which were fed a diet supplemented with 0, 170, 340, and 680 mg/kg gossypol acetate, respectively. After 60 days of feeding, the gossypol residue in the tissue, growth performance, blood biochemical indices, hepatopancreas histology, fatty acid components, and expression of key genes involved in lipid metabolism pathways were measured. It was found that the concentrations of free gossypol were increased significantly in the serum, bile, and hepatopancreas of carp fed 340 mg/kg and 680 mg/kg gossypol acetate (). Dietary gossypol acetate had a limited effect on growth performance, and high concentrations of gossypol acetate induced excessive hepatopancreatic fat deposition and hepatocyte injury in C. carpio. In addition, gossypol acetate decreased total polyunsaturated fatty acids (PUFAs) and docosahexaenoic acid in muscle. In the hepatopancreas, decreased HSL, PPARα, and CD36 may result in fat accumulation. In the muscle, decreased FADS2 may be the key reason for the decrease in PUFAs. Taken together, these findings indicated that dietary gossypol acetate can cause lipid metabolism disorders, such as hepatopancreatic damage and significant changes in tissue fatty acid profile, which are regulated by the key lipid metabolic genes in common carp.

CAS / MDL: 886-86-2
研究领域: 水产养殖 · 营养学 · 毒理学
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FOOD CHEMISTRY · 2025 · IF 9.8

Sustainable utilization of cottonseed meal: Integrated protein extraction and detoxification using deep eutectic solvents

Tian Wang,Dehai Yu,Jian Wang,Bo Yang,Lei Ma,Shuangjiao Xu

The growing demand for sustainable proteins has highlighted cottonseed meal (CSM) as a promising high-protein byproduct. Addressing the challenge of valorizing the annual global production of over 10 million tons of CSM in cottonseed processing, this study investigated the use of choline chloride-ethylene glycol deep eutectic solvent (DES-4) for efficient protein extraction from CSM while reducing toxic gossypol content. Through Box-Behnken response surface optimization, we established optimal conditions (56 °C/3 h/40% water) that achieved 86.85% protein yield while remarkably reducing bound gossypol content from 10.24 mg/g to 2.76 mg/g. Molecular dynamics simulations (MDS) revealed that DES-4 enhance protein recovery and gossypol separation through synergistic mechanisms involving stabilizing solubility, relaxing matrix structure, and disrupting complexes. The obtained protein (CSMP-E) demonstrated superior solubility, emulsifying properties, and antioxidant activity compared to alkali-extracted counterparts. Furthermore, hydrolyzed DES-extracted protein (CSMP-EH) exhibited enhanced DPP-IV inhibitory activity (IC 50  = 1.949 mg/mL), suggesting its potential for type 2 diabetes management.

研究领域: 食品科学 · 生物化学 · 可持续农业
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BIOMATERIALS · 2017 · IF 8.402

Versatile hyaluronic acid modified AQ4N-Cu(II)-gossypol infinite coordination polymer nanoparticles: Multiple tumor targeting, highly efficient synergistic chemotherapy, and real-time self-monitoring

Shihong Shen,Youshen Wu,Ke Li,Ya Wang,Jimin Wu,Yun Zeng,Daocheng Wu

A novel strategy for the preparation of infinite coordination polymer nanoparticles (ICPs) based nanomedicines was developed, with which hyaluronic acid modified AQ4N-Cu(II)-gossypol nanoparticles (HA@AQ4N-Cu(II)-gossypol NPs) were obtained. This is a highly efficient nanomedicine, in which gossypol serves as a chemotherapeutic agent and a self-carrier material; Cu(II) serves as the connecting point and anti-tumor enhancer; AQ4N not only serves as a chemotherapeutic agent and self-carrier material, but also as the self-monitor based on its inherent fluorescence. HA@AQ4N-Cu(II)-gossypol NPs possessed a spherical shape with a dynamic size of 88.7 ± 7.4 nm, and the total drug-loading content and drug encapsulation efficiency are 77.41% and 100%, respectively. This nanomedicine has a multiple tumor-targeting ability caused by HA-receptor mediation and pH-responsive drug release. A significantly low combination index (0.097) of AQ4N and gossypol is ascertained. In vivo experiments indicate that it accumulates and significantly releases drugs at the tumor region. With the use of only one-fiftieth of AQ4N and half of gossypol of the generally administered dose, they can achieve significantly high anti-tumor efficiency with negligible side effects. Importantly, the switching-type changed fluorescence of AQ4N can be used for in vivo real-time self-monitoring of the drug release and distribution, which allows us to adjust the administration dose and time for different tumor types and stages for individual therapy.

研究领域: 纳米医学 · 肿瘤学 · 药物递送系统
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NEOPLASIA · 2020 · IF 5.696

Gossypol inhibits cullin neddylation by targeting SAG-CUL5 and RBX1-CUL1 complexes

Qing Yu,Zhiguo Hu,Yanwen Shen,Yihan Jiang,Peichen Pan,Tingjun Hou,Zhen-Qiang Pan,Jing Huang,Yi Sun

Cullin-RING E3 ligase (CRL) is the largest family of E3 ubiquitin ligase, responsible for ubiquitylation of ∼20% of cellular proteins. CRL plays an important role in many biological processes, particularly in cancers due to abnormal activation. CRL activation requires neddylation, an enzymatic cascade transferring small ubiquitin-like protein NEDD8 to a conserved lysine residue on cullin proteins. Recent studies have validated that neddylation is an attractive anticancer target. In this study, we report the establishment of an Alpha-Screen-based high throughput screen (HTS) assay for in vitro CUL5 neddylation, and screened a library of 17,000 compounds including FDA approved drugs, natural products and synthetic drug-like small-molecule compounds. Gossypol, a natural compound derived from cotton seed, was identified as an inhibitor of cullin neddylation. Biochemical studies showed that gossypol blocked neddylation of both CUL5 and CUL1 through direct binding to SAG-CUL5 or RBX1-CUL1 complex, and CUL5-H572 plays a key role for gossypol binding. On cellular level, gossypol inhibited cullin neddylation in a variety of cancer cell lines and selectively caused accumulation of NOXA and MCL1, the substrates of CUL5 and CUL1, respectively, in multiple cancer cell lines. Combination of gossypol with specific MCL1 inhibitor synergistically suppress growth of human cancer cells. Our study revealed a previously unknown anti-cancer mechanism of gossypol with potential to develop a new class of neddylation inhibitors.

CAS / MDL: 303-45-7
研究领域: 药理学 · 肿瘤学 · 细胞生物学 · 分子生物学
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Food Bioscience · 2023 · IF 5.2

A novel Zn-MOF fluorescent probe for highly sensitive and rapid detection of gossypol in cottonseed oil and fetal bovine serum

Wenqing Li,Jinting Zhu,Xinru Qi,Changyan Sun,Wenjun Li,Zhidong Chang

Gossypol is a poisonous substance in cottonseed which seriously harms the internal organs, blood vessels, nerves, and reproductive systems of organisms. Therefore, detecting gossypol is of great significance in the field of food safety. This manuscript constructs a novel target-oriented gossypol fluorescence probe based on the energy competition absorption mechanism. The probe is a zinc-based metal organic framework material (Zn-MOF) with blue fluorescence, which can achieve rapid and sensitive detection of gossypol through fluorescence “turn-off” effect. It has the advantages of low detection limit (16.6 nM), ultra-fast response time (8 s), and favorable selectivity. Interestingly, this probe can be reused and the fluorescence can still be recovered after five cycles when detecting gossypol. In addition, the application of the fluorescent probe in cottonseed oil and fetal bovine serum is reliable, with the recovery of 99.35%–101.5% and the relative standard deviation of less than 2.72%. These results indicate that the developed sensor has prominent application potential in the field of food and biological detection.

研究领域: 分析化学 · 食品科学 · 生物检测
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ADVANCED FUNCTIONAL MATERIALS · 2022 ·Vol. 32 ·期 28 ·2201666 · IF 19.924

Molecular Stacking Composite Nanoparticles of Gossypolone and Thermodynamic Agent for Elimination of Large Tumor in Mice via Electrothermal-Thermodynamic-Chemo Trimodal Combination Therapy

Yiming Liu,Peng Tang,Peng Xiao,Siyuan Luo,Shuangxi Zhang,Hui Zhang,Yuexuan Yang,Daocheng Wu

To further improve the comprehensive therapeutic effect for large tumors, tumor cell membrane-camouflaged molecular stacking composite nanoparticles (APGn@Mem NPs) are prepared by molecular stacking of chemotherapeutic drug gossypolone (Gn), thermodynamic agent (2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH)), polyvinyl alcohol, and phase change material lauric acid, which show a clear core–shell structure with a size of 65 ± 9.8 nm, high drug loading, low toxicity, homologous targeting, and thermal-responsive release property. A type of micro-electrothermal needle (MEN) with precise temperature control in situ (temperature range: mean value T ± 7 °C) is designed as the assistant heating system for APGn@Mem NPs. Subsequently, an elaborate tumor combination therapy strategy of electrothermal-thermodynamic-chemo trimodal combination therapy is developed through APGn@Mem NPs combined with the temperature control of MEN. Under MEN heating in situ, AIPH is rapidly released and generates abundant free radicals for short-term electrothermal and thermodynamic therapy, while the release of Gn is relatively slow for long-term chemotherapy. For large tumors (≈300 mm 3 ) of nude mice, such combination therapy achieves remarkable comprehensive therapeutic efficacy with the 16-day tumor inhibition rate of 99.89% and the 60-day tumor recurrence rate of 20%, indicating this combination therapy has the prominent advantage and potential application in future.

研究领域: 纳米医学 · 肿瘤学 · 生物材料
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ADVANCED FUNCTIONAL MATERIALS · 2021 ·Vol. 31 ·期 24 ·2100954 · IF 18.808

IR780-Loaded Hyaluronic Acid@Gossypol–Fe(III)–EGCG Infinite Coordination Polymer Nanoparticles for Highly Efficient Tumor Photothermal/Coordinated Dual Drugs Synergistic Therapy

Siyuan Luo,Ya Wang,Shihong Shen,Peng Tang,Zeying Liu,Shuai Zhang,Daocheng Wu

A novel strategy called “two-stage dual-synergistic tumor therapy (TDTT),” which combines photothermal therapy with infinite coordination polymers (ICPs) chemotherapy at the first stage in the short term and two drugs of ICPs synergistic chemotherapy (coordinated dual drugs chemotherapy) at the second stage in the long term, is proposed. This strategy is achieved by preparing IR780-loaded hyaluronic acid (HA) encapsulated gossypol–Fe(III)–epigallocatechin gallate (EGCG) ICP nanoparticles (HA@IRGFE ICP NPs), which have IR780 inclusions, a natural gossypol, and EGCG coordinated with Fe 3+ framework, and a HA shell. It is found that the HA@IRGFE ICP NPs’ diameter is 120.0 ± 39.5 nm and has tumor-targeting ability and can be rapidly released in tumor environment. Their photothermal conversion efficiency is greatly improved to 47.8%, and the total combination index of TDTT is 0.38, which indicates an excellent synergistic therapy result. These HA@IRGFE ICP NPs show low toxicity with a high tolerated dose (30.0 mg kg −1 ), a high tumor inhibition rate of 98.7%, and a very low tumor recurrence rate over 60 days (12.5%) with TDTT strategy, indicating their great potential applications in the field of tumor therapy.

CAS / MDL: 989-51-5
研究领域: 生物医学工程 · 纳米医学 · 肿瘤学
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