Green extraction is aimed at reducing energy consumption by using renewable plant sources and environmentally friendly bio-solvents. Lime (Citrus aurantifolia) is a rich source of flavonoids (e.g., hesperidin) and limonoids (e.g., limonin). Manufacturing of lime products (e.g., lime juice) yields a considerable amount of lime peel as food waste that should be comprehensively exploited. The aim of this study was to develop a green and simple extraction method to acquire the highest yield of both limonin and hesperidin from the lime peel. The study method included ethanolic-aqueous extraction and variable factors, i.e., ethanol concentrations, pH values of solvent, and extraction temperature. The response surface methodology was used to optimize extraction conditions. The concentrations of limonin and hesperidin were determined by using UHPLC-MS/MS. Results showed that the yields of limonin and hesperidin significantly depended on ethanol concentrations and extraction temperature, while pH value had the least effect. The optimal extraction condition with the highest amounts of limonin and hesperidin was 80% ethanol at pH 7, 50 °C, which yields 2.072 and 3.353 mg/g of limonin and hesperidin, respectively. This study illustrates a green extraction process using food waste, e.g., lime peel, as an energy-saving source and ethanol as a bio-solvent to achieve the highest amount of double bioactive compounds.

Lime peels are food waste from lime product manufacturing. We previously developed and optimized a green extraction method for hesperidin-limonin-rich lime peel extract. This study aimed to identify the metabolomics profile of phytochemicals and the anti-cancer effects of ethanolic extract of lime (Citrus aurantifolia) peel against liver cancer cells PLC/PRF/5. The extract’s metabolomics profile was analyzed by using LC-qTOF/MS and GC-HRMS. The anti-cancer effects were studied by using MTT assay, Annexin-PI assay, and Transwell-invasion assay. Results show that the average IC₅₀(s) of hesperidin, limonin, and the extract on cancer cells’ viability were 165.615, 188.073, and 503.004 µg/mL, respectively. At the IC₅₀ levels, the extract induced more apoptosis than those of pure compounds when incubating for 24 and 48 h (p < 0.0001). A combination of limonin and hesperidin showed a synergistic effect on apoptosis induction (p < 0.001), but the effect of the combination was still less than that of the extract at 48 h. Furthermore, the extract significantly inhibited cancer cell invasion better than limonin but equal to hesperidin. At the IC₅₀ level, the extract contains many folds lower amounts of hesperidin and limonin than the IC₅₀ doses of the pure compounds. Besides limonin and hesperidin, there were another 60 and 22 compounds detected from the LCMS and GCMS analyses, respectively. Taken altogether, the superior effect of the ethanolic extract against liver cancer cells compared to pure compound likely results from the combinatorial effects of limonin, hesperidin, and other phytochemical components in the extract.

Bergaptol (5-hydroxypsoralen or 5-hydroxyfuranocoumarin) is a naturally occurring furanocoumarin widely found in citrus fruits, which has multiple health benefits. Nonetheless, no specific review articles on bergaptol have been published. Compiling updated information on bergaptol is crucial in guiding future research direction and application. The present review focuses on the research evidence related to the pharmacological properties and toxicity of bergaptol. Bergaptol has anti-inflammatory, antioxidant, anti-cancer, anti-osteoporosis, anti-microbial, and anti-lipidemic effects. It can inhibit the activities of cytochrome P450s (CYP), especially CYP2C9 and CYP3A4, thereby affecting the metabolism and concentrations of some drugs and toxins. Compared with other coumarins, bergaptol has the least potency to inhibit CYP3A4 in cancer cells. Instead, it can suppress drug efflux transporters, such as P-glycoprotein, thereby overcoming chemotherapeutic drug resistance. Furthermore, bergaptol has antimicrobial effects with a high potential for inhibition of quorum sensing. In vivo, bergaptol can be retained in plasma for longer than other coumarins. Nevertheless, its toxicity has not been clearly reported. In vitro study suggests that, unlike most furocoumarins, bergaptol is not phototoxic or photomutagenic. Existing research on bergaptol has mostly been conducted in vitro. Further in vivo and clinical studies are warranted to identify the safe and effective doses of bergaptol for its multimodal application.

Glucosinolates in Brassica vegetables can be hydrolyzed into various products, e.g., chemopreventive agents, isothiocyanates (ITCs) and anti-thyroid substance, goitrin. Cooking can reduce goitrin but destroy isothiocyanates. This study aimed to optimize cooking conditions for reducing goitrin while preserving isothiocyanates in Brassica vegetables. Cabbage and Chinese kale samples were divided evenly into raw, blanched, steamed, and water-based stir-fried samples. Cooking temperature and time were varied at 60, 80, or 100 °C for 2, 4, or 6 min. The levels of goitrin, benzyl isothiocyanate (BITC), and sulforaphane (SFN) were measured using LC-MS/MS. Response surface model (RSM) was used to identify the optimal cooking conditions to reduce goitrin but preserve ITCs. Results showed that goitrin content in cabbage depended on the cooking methods, temperature, and time, while that of Chinese kale only depended on the methods. In contrast, the concentrations of SFN in cabbage and BITC in kale depended on the cooking temperature and time but not methods. Based on RSM analysis, the suggested household cooking methods for preserving isothiocyanates and reducing goitrin are steaming cabbage at 80–100 °C for 4 min and stir-frying Chinese kale at 60–100 °C for 2 min. Such methods may preserve the bioactive compounds while reducing food hazards.

In brewing coffee, a huge amount of food waste is generated; that waste, coffee husks in particular, should be comprehensively exploited. They offer a rich source of bioactive compounds such as caffeine, chlorogenic acid, and trigonelline. The aim of this study was to investigate the effects of extraction methods on the bioactive compounds and antioxidant activity of such waste. Coffee husks in this study were fermented with S. cerevisiae based on a solid-state fermentation technique. The study method included ethanolic or water extraction with varied controllable factors, i.e., temperature (60, 100°C) and extraction technique. Bioactive contents were investigated with the FolinCiocalteu assay and ¹H-NMR spectroscopy. The antioxidant activity was investigated with DPPH and FRAP assays. Results show that yields were the highest in the extract of fermented coffee husks at 100°C. The highest levels of bioactive contents (total trigonelline content at 3.59 and antioxidant activity at 23.35 (DPPH) and 25.9 (FRAP)) were found in the ethanolic extract of fermented coffee husks at 60°C. The bioactive content and bioactivity, including antioxidant activity, depended on different raw materials, preparation methods, and extraction conditions. This study illustrates the potential for using food waste such as coffee husks as a sustainable source of bioactive compounds or bioactive extracts.