BACKGROUND: Dietary supplements derived from botanicals are commonly consumed and investigated in biomedical studies for their potential health benefits. Accurate identification and quantification of key chemical constituents from botanical ingredients is necessary for consistent product preparations and reproducible research results. Manufacturers need quantitative reference materials of the chemical constituents of interest to verify the content of ingredients and products. The rigor and reproducibility of biomedical research is enhanced through thorough characterization of the interventions used in mechanistic, clinical, and safety investigations. Quantitative reference materials enable reliable product quality assessments and reproducible research results.
OBJECTIVE: Solution-based certified reference material (CRM) mixes were developed as calibrants for phytochemicals in ginger and kava. The kava CRM contained yangonin, desmethoxyyangonin, dihydrokavain, DL-kavain, methysticin, dihydromethysticin, flavokawain A, flavokawain B, and flavokawain C. The ginger CRM contained 6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, 8-shogaol, and 10-shogaol.
METHODS: Each phytochemical was sourced as an isolated compound and assigned a purity factor by a mass balance approach accounting for residual impurities. The solution standard mixes were formulated by gravimetric addition of each phytochemical incorporating the purity factor and diluting with acetonitrile to the target concentrations of 500 µg/mL for the gingerols and shogaols, 250 µg/mL for the kavalactones, and 25 µg/mL for the flavokawains.
RESULTS: The concentration accuracy of each component in the solution mixes was analytically verified by ultra high performance liquid chromatography with ultraviolet detection (UHPLC-UV) assay comparison to an independently prepared calibration solution. Each component in the ginger and kava CRMs were within 5 and 7% of the target concentrations, respectively.
CONCLUSIONS: Homogeneous kava and ginger phytochemical solution mixes were produced with accurate constituent concentrations and demonstrated good stability over 2 years. These solution mixes were launched as commercially available CRMs.
CONCLUSIONS: These mixes can be used as accurate concentration stock solutions to prepare calibrators and controls for botanical dietary supplement product testing and standardization.

The dynamically evolving science of pharmacology requires AI technology to advance a new path for drug development. The author proposes generative AI for future drugs, identifying suitable drug molecules, uncharacteristically to previous generations of medicines, incorporating the wisdom, experience, and intuit of traditional materia medica and the respective traditional medicine practitioners. This paper describes the guiding principles of the new drug development, springing from the tradition and practice of Tibetan medicine, defined as the Interactive Nutrient Process (INP). The INP provides traditional knowledge and practitioner\'s experience, contextualizing and teaching the new drug therapy. An illustrative example of the outcome of the INP is a potential small molecule drug, 6-Shogaol and related shogaol derivatives, from ginger roots (Zingiber officinalis fam. Zingiberaceae) evaluated clinically for 12 months for biological markers of iron homeostasis in patients with the myelodysplastic syndromes (MDS). The study\'s preliminary results indicate that 6-Shogaol and related shogaols may improve iron homeostasis in low-risk/intermediate-1 MDS patients without objective or subjective side effects.

Gingerols represent the main bioactive compounds in ginger drugs mostly Zinigiber officinale (F. Zingebraceae) and account for the biological activities and the strong/pungent flavor in ginger. Ginger (Z. officinale) rhizome is one of the most valued herbal drugs for ailments\' treatment in many ayurvedic medicine asides from its culinary applications as a spice. Gingerols and their dehydrated products shogaols are phenolic phytochemicals found in members of the Zingiberaceae family and account for most of their effects including anti-inflammatory and anticancer activities. This review entails most of the novel trends related to the extraction, optimization, and formulations of gingerols and shogaols to insure best recoveries and efficacies from their natural resources. Further, it presents a comprehensive overview of the different analytical approaches for the determination of gingerols/shogaols\' levels in nutraceuticals to ensure highest quality and for their detection in body fluids for proof of efficacy.

Bioavailability is critical in ensuring bioefficacy of ginger compounds, which have not been studied in chicks. In this study, day-old chicks were treated with ginger root extract at 0.0, 0.4, 0.8, 1.5, and 3.0% for 42 days. The gingerols and shogaols in chick samples were analyzed by liquid chromatography-mass spectrometry. The primary phase-I metabolic pathway for gingerols and shogaols was the reduction of ketone groups into hydroxyl groups. Shogaols were also metabolized through thiol conjugation and hydrogenation of double-bond pathways. Within the bloodstream, gingerols and their metabolites predominantly existed as glucuronidate or sulfate conjugates. However, the levels of the free form and conjugates were comparable for shogaols. In breast meat, the quantities of both the free form and conjugates for all compounds were similar. In plasma, more than 50% of absorbed 6-gingerol (6G) and 90% of absorbed 6-shogaol underwent reduction to their respective metabolites. However, in breast meat, the percentage of reduction for absorbed 6G was less than 50%, and for absorbed 6-shogaol, it was less than 60%. Ginger compounds were absorbed into chick plasma ranging from 1.4 to 8.5 μg/mL and breast meat ranging from 7.1 to 114.6 μg/100 g across the 0.4-3.0% dose range in a dose-dependent manner.

Zingiber officinale Roscoe is an excellent source of bioactive compounds, mainly gingerols and shogaols compounds, that associated with various bioactivities including antioxidant, anticancer, anti-inflammatory, antimicrobial, and antibiofilm. Zingiber officinale Roscoe found its application in the food, pharmaceutical, and cosmeceutical industries. The demand for a high quality of ginger oleoresin extracts based on the contents of gingerols and shogaols compounds for a health-benefit has dramatically increased. Various extraction techniques, including the conventional and advanced extraction techniques for gingerols and shogaols have been reported based on the literature data from 2012 to 2022. The present review examines the functional composition and bioactivities of Zingiber officinale Roscoe and the advanced green extraction technologies. Some variations in the quantity and quality of gingerols and shogaols compounds are because of the extraction method employed. This review provides a depth discussion of the various green advanced extraction technologies and the influences of process variables on the performance of the extraction process. Lower temperature with a short exposure time such as ultrasound-assisted and enzyme-assisted extraction, will lead to high quality of extracts with high content of 6-gingerol. High thermal processing, such as microwave-assisted and pressurized liquid extraction, will produce higher 6-shogaol. Meanwhile, supercritical fluid extraction promotes high quality and the safety of extracts by using non-toxic CO2. In addition, challenges and future prospects of the extraction of ginger oleoresin have been identified and discussed. The emerging green extraction methods and technologies show promising results with less energy input and higher quality extracts than conventional extraction methods.

This study aimed to investigate whether hot-melt extrusion (HME) processing can promote molecular encapsulation of a multi-component natural product composed of volatile and pungent hydrophobic substances (ginger oleoresin (OR)) with cyclodextrins. 6-Gingerol and 6-shogaol, the biomarkers of ginger OR, were quantified by HPLC. Phase-solubility studies were performed using β-cyclodextrin (βCD) and hydroxypropyl-β-cyclodextrin (HPβCD) for ginger OR complexation. Solid complexes were then prepared by thermal (HME)- and solvent (slurry (SL))-based methods. Morphology, thermal behavior, solubility, in vitro dissolution, and in vivo anti-inflammatory activity were evaluated. HPβCD gave rise to AL-type complexes with ginger OR, whereas βCD led to materials with limited solubility. Ginger OR was complexed with HPβCD by HME without significant change in gingerol and shogaol content. Additionally, thermogravimetric analysis (TGA) suggested higher volatile retention in HME complexes than in SL ones. Shogaol and gingerol solubility and dissolution significantly increased from SL and HME complexes compared with ginger OR. In turn, 1:2 OR/HPβCD HME complex showed higher 6-shogaol solubility than SL, associated with a gradual release. The carrageenan-induced pleurisy test showed that the anti-inflammatory activity of ginger OR was maintained after complexation with HPβCD. The complexes significantly decrease the levels of IL-1β and inhibit cell migration. HME complex showed performance equivalent to the positive control and superior to the SL material. Taken together, these results indicate that HME can be useful for promoting the molecular encapsulation of complex natural products that contain volatile and thermolabile substances. HME complexes showed better in vivo and in vitro performance than complexes prepared using the solvent-based method.

Liquid chromatography-mass spectrometry (LC-MS)-based metabolomics has become an important tool to increase our understanding of how diet affects human health. However, public and commercial mass spectral libraries of dietary metabolites are limited, resulting in the greatest challenge in converting mass spectrometry data into biological insights. In this study, we constructed an LC-MS/MS ginger library as an example to demonstrate the importance of dietary libraries for discovering food biomarkers. The functional and exposure biomarkers of ginger were investigated using plasma samples from mice treated with control and ginger extract diets. Our results showed clear discrimination between the metabolome of mice on normal and ginger extract diets. Using the in-house ginger library, we identified 20 ginger metabolites that can be used as exposure biomarkers of ginger. However, without the LC-MS/MS ginger library, none of the ginger metabolites could be accurately identified based on online mass databases. In addition, ginger treatment significantly impacts the endogenous metabolome, especially the purine metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis. Overall, we demonstrated that the construction of LC-MS/MS spectra dietary libraries would enhance the ability to identify potential dietary biomarkers and correlate potential health benefits associated with food consumption.

The discovery of eco-friendly plant-based insecticides is currently booming in research with an attempt to replace synthetic chemical insecticides causing tremendous adverse effects. The present work studied the insecticidal potential of ginger, an important medicinal plant. Four crude extracts from Zingiber officinale rhizomes were evaluated for their contact toxicity against second instars of Spodoptera litura, Spodoptera exigua and Spodoptera frugiperda using the topical application. The hexane extract exhibited the strongest toxicity to S. exigua with the LD50 of 9.92 and 8.40 µg/larva at 24 and 48 h posttreatment, respectively, followed by S. frugiperda. Comparative toxicity of the most abundant secondary metabolites from the hexane extract, gingerols and shogaols, against both insects concluded that 8-shogaol (5) was identified as the most active compound against S. frugiperda with the LD50 of 7.68 and 3.96 µg/larva at 24 and 48 h posttreatment, respectively.

Ginger is best known for its aromatic odour, spicy flavour and health-benefiting properties. Its flavour is derived primarily from two compound classes (gingerols and shogaols), with the overall quality of the product depending on the interaction between these compounds. Consequently, a robust method for determining the ratio of these compounds would be beneficial for quality control purposes. This study investigated the feasibility of using hyperspectral imaging to rapidly determine the ratio of 6-gingerol to 6-shogoal in dried ginger powder. Furthermore, the performance of several pre-processing methods and two multivariate models was explored. The best-performing models used partial least squares regression (PSLR) and least absolute shrinkage and selection operator (LASSO), using multiplicative scatter correction (MSC) and second derivative Savitzky-Golay (2D-SG) pre-processing. Using the full range of wavelengths (~400-1000 nm), the performance was similar for PLSR (R2 ≥ 0.73, RMSE ≤ 0.29, and RPD ≥ 1.92) and LASSO models (R2 ≥ 0.73, RMSE ≤ 0.29, and RPD ≥ 1.94). These results suggest that hyperspectral imaging combined with chemometric modelling may potentially be used as a rapid, non-destructive method for the prediction of gingerol-to-shogaol ratios in powdered ginger samples.

Context: Carbonized ginger, a type of charry herb, has been used as a hemostatic medicine since ancient times. However, there are some serious problems such as inhomogeneous heating and emitting smoke during processing with traditional stir-frying method.Objective: To investigate the feasibility to obtain carbonized ginger by stir-frying with sand instead of stir-frying method.Materials and methods: Dried-ginger (100 g) was processed by stir-frying for 30 min at 270 ± 10 °C, or by stir-frying with sand (1:10, w/w) for 8 min at 240 ± 5 °C. The HPLC fingerprint was established for two samples. The adsorption capacity and major components including tannins, gingerols, shogaols and gingerone were quantitated by UV and HPLC, respectively. The hemostatic effect by prothrombin time (PT) and activated partial thromboplastin time (APTT) was evaluated in vitro.Results: The similarity of the two samples for HPLC fingerprints was >0.93. The sand-fried samples showed significantly higher adsorption capacity compared with the stir-fried samples (4.915 vs. 4.593 mg/g; p < 0.05) and higher contents of major components (4.698 vs. 3.930 mg/g, 1.352 vs. 1.144 mg/g, 2.419 vs. 2.095 mg/g, 0.666 vs. 0.568 mg/g and 1.083 vs. 0.911 mg/g for tannins, gingerone, 6-shogaol, 8-shogaol and 10-shogaol, respectively; p < 0.05); while no significant differences were seen for 6-gingerol, 8-gingerol and 10-gingerol (p > 0.05). The PT and APTT values were similar between the stir-fried and sand-fried test groups and significantly lower compared to controls (p < 0.05).Conclusions: The carbonizing process by stir-frying with sand is superior to the stir-frying method for carbonized ginger.