Search Results (179)

In this study, using 70% anhydrous ethanol as the extraction solvent, Moringa oleifera Lam. seed powder was extracted with the microwave-assisted extraction method, followed by purification using macroporous adsorbent resin NKA-9. The purified glucosinolate was subsequently hydrolyzed with myrosinase. The glucosinolate and its enzymatic product were identified as 4-(α-L-rhamnopyranosyloxy) benzyl glucosinolate (4-RBMG) and benzyl isothiocyanate (BITC) by UV–Vis, FT-IR, NMR, and MS. The bioactivities, including anti-oxidation, anti-inflammation, and anti-tumor activities of 4-RBMG and BITC, were systematically evaluated and compared. The results show that at 5–20 mg/mL, the anti-oxidation effects of 4-RBMG on DPPH and ABTS free radicals are superior to those of BITC. However, at the same concentrations, BITC has stronger anti-inflammatory and anti-tumor activities compared to 4-RBMG. Notably, at a concentration of 6.25 μmol/L, BITC significantly inhibited NO production with an inhibitory rate of 96.67% without cytotoxicity. Additionally, at a concentration of 40 μmol/L, BITC exhibited excellent inhibitory effects on five tumor cell lines, with the cell inhibitory rates of leukemia HL-60, lung cancer A549, and hepatocellular carcinoma HepG2 exceeding 90%. This study provides some evidence that the enzymatic product, BITC, shows promise as a therapeutic agent for tumor suppression and inflammation reduction. Full article

In this study, 3-chlorothiophene-2-carboxylic acid (HL) was used as a main ligand to successfully synthesize four novel complexes: [Cu(L)₂(Py)₂(OH₂)₂] (1), [Co(L)₂(Py)₂(OH₂)₂] (2) (Py = pyridine), [{Ni(L)₂(OH₂)₄}₂{Ni(L)(OH₂)₅}]L•5H₂O (3), and [{Co(L)₂(OH₂)₄}₂{Co(L)(OH₂)₅}]L•5H₂O (4). All four compounds were identified by elemental analysis and ESI mass spectrometry, and subsequently characterized by IR spectroscopy, UV-visible diffuse reflectance spectroscopy, electron paramagnetic resonance spectroscopy, thermogravimetric analysis, single-crystal X-ray crystallography, and cyclic voltammetry. X-ray analyses revealed that complexes 1 and 2 exhibit a centrosymmetric pseudo-octahedral coordination geometry; the copper (II) and cobalt (II) metal ions, respectively, are located at the crystallographic center of inversion. The coordination sphere of the copper (II) complex is axially elongated in accordance with the Jahn–Teller effect. Intriguingly, for charge neutrality, compounds 3 and 4 crystallized as three independent mononuclear octahedrally coordinated metal centers, which are two $\left[\mathrm{M}{\mathrm{L}}_2{\left({\mathrm{O}\mathrm{H}}_2\right)}_4\right]$ complex molecules and one ${\left[\mathrm{M}\mathrm{L}{\left({\mathrm{O}\mathrm{H}}_2\right)}_5\right]}^{+}$ complex cation (M = ${\mathrm{N}\mathrm{i}}^{\mathrm{I}\mathrm{I}}$ and ${\mathrm{C}\mathrm{o}}^{\mathrm{I}\mathrm{I}}$, respectively), with the ligand anion ${\mathrm{L}}^{-}$ serving as the counter ion. The anticancer activities of these complexes were systematically assessed on human leukemia K562 cells, lung cancer A549 cells, liver cancer HepG2 cells, breast cancer MDA-MB-231 cells, and colon cancer SW480 cells. Among them, complex 4 shows significant inhibitory effects on leukemia K562 cells and colon cancer SW480 cells. Full article

In this study, we aimed to investigate the effect of Engeletin (ENG) on insulin resistance and the associated oxidative cell damage in human HepG2 liver cells. The cells were grown in a cell culture medium, and insulin resistance was induced. After the determination of the toxic and effective doses of Engeletin, the effects of Engeletin on insulin resistance and insulin resistance-induced oxidative damage, inflammation, and apoptosis. To induce IR, culture plates were treated with 30 mM glucose and 50 nM insulin and incubated for 48 h. Engeletin and metformin were given one hour before starting the insulin resistance induction. In the HepG2 cells, insulin resistance decreased glucose consumption, the expression of ISR-1 and ISR-2, and the GLUT-2 levels, while they were all increased by Engeletin, which showed a metformin-like effect. In addition, Engeletin alleviated oxidative cell damage by decreasing MDA levels, which increased due to insulin resistance-induced oxidative stress, increasing the GSH and SOD levels and decreasing the caspase-3 (Cas-3), caspase-9 (Cas-9), and tumor necrosis factor alpha (TNF-α) levels, which also increase under insulin resistance conditions. Engeletin was found to have the protective and therapeutic effect of reducing insulin resistance (IR) and the oxidative cell damage it causes in human HepG2 cells. Full article

Heterocyclic compounds have shown that they hold significant therapeutic activities, highlighting the importance of discovering and developing novel candidates against cancers, infections, and oxidative stress-associated disorders. In this study, we demonstrated the biological activity of our previously synthesized thiazolidinone derivatives (TZDs-1, 6, and 7). Furthermore, we synthesized and structurally characterized a new derivative (TZD-5) using IR, ¹H NMR, and ¹³C NMR spectroscopy, confirming the presence of its key functional groups, namely, carbonyl and imine. Their antioxidant activity was assessed through the DPPH assay, with TZD-5 showing the most potent effect (IC₅₀ = 24.4 µg/mL), comparable to ascorbic acid, an effect attributed to the methoxy group introduced via N-alkylation. Cytotoxicity was evaluated using the MTS assay on normal (HFF-1) and cancerous (HepG2 and A549) cell lines at two time points: 24- and 48 h exposure. Our findings highlight clear differences in cytotoxicity and selectivity among the tested thiazolidinone derivatives. TZD-1 and TZD-6 demonstrated significant, dose-dependent cytotoxic effects on both cancerous (HepG2 and A549) and normal (HFF-1) cell lines, thus limiting their therapeutic potential due to insufficient selectivity. TZD-5 exhibited moderate selectivity with higher susceptibility for HepG2 cells compared to normal cells. Notably, TZD-7 showed the most favorable cytotoxic profile, demonstrating strong selective cytotoxicity toward cancer cell lines with minimal adverse effects on normal fibroblasts. Overall, the results highlight TZD-5 and TZD-7 as promising candidates for antioxidant and selective anticancer therapies. Full article

The effects of soy protein and whey protein supplementation on glycemic control show inconsistency, and the mechanisms underlying the impact of a high-protein diet on blood glucose regulation remain unclear. This study aimed to explore the impact of a dual-protein (DP) blend comprising soy protein isolate (SPI) and whey protein concentrate (WPC), processed through high-pressure homogenization, on mice with Type 2 diabetes mellitus (T2DM) and its potential mechanisms. In the in vitro experiments, an insulin-resistant (IR) HepG2 cell model was treated with DP, resulting in a significant enhancement of glucose uptake and upregulation of IRS1 and GLUT4 expression. For the in vivo experiments, male C57BL/6J mice were randomly assigned into four groups (n = 6) based on body weight: normal control, T2DM model group, Metformin-treated group, and DP-treated group. Following a 5-week feeding period, Metformin and DP significantly reduced levels of blood sugar, AUC, TC, TG, and LDL-C in T2DM mice. Additionally, TP and ALB levels in the DP group were notably higher in the model group. In the liver and pancreas, DP alleviated histopathological changes and promoted liver glycogen synthesis in T2DM mice. Moreover, the levels of IRS1 and PI3K in the livers of mice in the DP group were significantly higher than those in the model group. Compared with the model groups, DP significantly reduced the expression of CD45 and increased the expression of CD206 in the pancreas of mice. Furthermore, 16S rRNA analysis revealed that DP altered the composition of the gut microbiota in diabetic mice, increasing the relative abundance of Lactobacillus, Parvibacter, and Lactobacillaceae. This suggested that DP could alleviate functional metabolic disorders in the gut and potentially reverse the risk of related complications. In conclusion, soy whey dual-protein may have an effective nutritional therapeutic effect on T2DM mice by regulating lipid metabolism, the INS/IRS1/PI3K signaling pathway, and gut microbiota. Full article

Background/Objectives: Endophytes can produce bioactive metabolites similar to their host plants. CM-YJ44 (Pseudomonas protegens CHA0, 99.24% similarity), an endophyte from Dendrobium officinale, has not yet validated hypoglycemic potential. This study aimed to evaluate its anti-insulin resistance (IR) activity and metabolite profile. Methods: The fermentation broth of CM-YJ44 was separated into three fractions (CM-YJ44-1, -2, and -3) using semi-preparative high-performance liquid chromatography (pre-HPLC). An IR HepG2 cell model was constructed to evaluate their glucose uptake capacity. CM-YJ44-3 was further tested for oxidative stress, inflammatory, and insulin signaling pathway activation. Metabolites in CM-YJ44-3 were preliminarily identified using the Q Exactive Focus LC-MS system (QE), and the dendrobine content was quantified by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Molecular docking was performed to predict the binding affinities between dendrobine and target proteins. Results: Among the three fractions, CM-YJ44-3 significantly reduced nitric oxide (NO) and reactive oxygen species (ROS) levels in IR cells, enhanced glycogen synthesis, upregulated the activities of pyruvate kinase (PK) and hexokinase (HK), and suppressed the expression of inflammatory factors. Its mechanism of action was mainly through activation of the IRS1/PI3K/Akt/GSK3β/GLUT4 signaling pathway. QE analysis preliminarily identified 24 metabolites in CM-YJ44-3. Quantitative analysis by UPLC-MS/MS showed that the dendrobine content was 78.73 ± 4.29 ng/mL. Molecular docking results indicated that dendrobine exhibited binding energies below −5 kcal/mol with multiple target proteins involved in this signaling pathway, suggesting it may be a key bioactive component responsible for the anti-IR effect. Conclusions: This study provides the first evidence of hypoglycemic bioactive metabolite production by strain CM-YJ44, indicating its potential as a novel microbial candidate for alleviating IR. Full article

Metabolic syndrome (MetS) poses considerable toxicological risks due to its association with an increased likelihood of metabolic dysfunction-associated steatotic liver disease (MASLD), and is characterized by hypertension, hyperglycemia, dyslipidemia, and obesity. This study aimed to investigate the therapeutic potential of flavonoid-rich lotus seedpod extract (LSE) in alleviating MetS and MASLD-related hepatic disturbances. In vivo, mice subjected to a high-fat diet (HFD) and streptozotocin (STZ) injection were supplemented with LSE or simvastatin for 6 weeks. Obesity indicators included body weight and epididymal fat, while insulin resistance was measured by fasting serum glucose, serum insulin, homeostasis model assessment–insulin resistance index (HOMA-IR), and oral glucose tolerance (OGTT). Also, the levels of serum lipid profiles and blood pressure were evaluated. Adipokines, proinflammatory cytokines, liver fat droplets, and peri-portal fibrosis were analyzed to clarify the mechanism of MetS. LSE significantly reduced the HFD/STZ-induced MetS markers better than simvastatin, as demonstrated by hypoglycemic, hypolipidemic, antioxidant, and anti-inflammatory effects. In vitro, LSE improved oleic acid (OA)-triggered phenotypes of MASLD in hepatocyte HepG2 cells by reducing lipid accumulation and enhancing cell viability. This effect might be mediated through proteins involved in lipogenesis that are downregulated by adenosine monophosphate-activated protein kinase (AMPK). In addition, LSE reduced reactive oxygen species (ROS) generation and glycogen levels, as demonstrated by enhancing insulin signaling involving reducing insulin receptor substrate-1 (IRS-1) Ser307 phosphorylation and increasing glycogen synthase kinase 3 beta (GSK3β) and protein kinase B (PKB) expression. These benefits were dependent on AMPK activation, as confirmed by the AMPK inhibitor compound C. These results indicate that LSE exhibits protective effects against MetS-caused toxicological disturbances in hepatic carbohydrate and lipid metabolism, potentially contributing to its efficacy in preventing MASLD or MetS. Full article

The aim of this study was to investigate the hypoglycemic activity and mechanism of G. lemaneiformis polysaccharide gels (GLP and GLP-HV) based on IR/IRS-2/PI3k/Akt/Glut4 and glycometabolism signaling pathways in HepG2 cells. After H₂O₂-Vc degradation, the molecular weight of G. lemaneiformis polysaccharide gel declined from 1478 kDa to 16 kDa. Molecular weight chromatogram and distribution indicated that GLP-HV had a high molecular weight homogeneity compared to GLP. G. lemaneiformis polysaccharide gels significantly decreased the TC, TG, LDL-C, MDA, and LDH contents and enhanced the activities of HDL-C, T-AOC, CAT, GSH-PX, SOD, insulin, and glycogen in HepG2 cells. Fluorescent staining results showed that G. lemaneiformis polysaccharide gels reduced ROS and calcium ions levels in HepG2 cells. GLP and GLP-HV displayed excellent hypoglycemic activity, with GLP-HV performing better. Furthermore, qPCR and Western blot analysis revealed that G. lemaneiformis polysaccharide gels remarkably strengthened the levels of IR, IRS-2, PI3K, Akt, Glut4, HK, G6PD, PFK, PEPCK, GK, PK genes, and proteins. Spearman’s correlation analysis revealed that the IR/IRS-2/PI3k/Akt/Glut4 signaling pathway played a dominant role in regulating activity. These results show that G. lemaneiformis polysaccharide gels present a prominent hypoglycemic effect mediated by the IR/IRS-2/PI3k/Akt/Glut4 and glycometabolism signaling pathways, with the former playing a dominant role. Full article

The rising demand for alternative solutions to diabetes mellitus has prompted significant interest in the exploration of plant-derived anti-diabetic compounds, especially within a circular economy framework that seeks sustainable and profitable reuse options. In this context, red (RSGO) and white (WGSO) grape seed oils, by-products of Sicilian vineyards, were prepared, analyzed for their fatty acid, polyphenol, carotenoid, and chlorophyll content, and evaluated for their glucose-lowering ability on HepG2 cells. Utilizing cytochemical techniques, flow cytometry, and protein blotting, we explored the effects of non-toxic oil dilutions on (i) glycogen storage, (ii) glucose consumption/uptake, (iii) GLUT-2, GLUT-4, and hepatocyte nuclear factor-1α (HNF1α) expression levels, and (iv) AMP-activated protein kinase (AMPK), insulin receptor substrate-1 (IRS-1), AKT, and PKCζ phosphorylation states, which are involved in insulin-mediated and -independent regulation of GLUT-4 membrane exposure. RGSO and WGSO, despite adopting slightly varying molecular strategies, were both proven to be effective stimulators of glucose absorption and glycogenesis. Specifically, RSGO promoted GLUT-2 and GLUT-4 up-regulation, whereas the WGSO-induced effect was associated with an increase in GLUT-4 levels alone. Moreover, the oils activated both pathways responsible for GLUT-4 translocation. Therefore, these wine-making residues have substantial potential as anti-diabetic solutions, holding promise for integration into the biomedical and food sectors. Full article

Three new complexes of copper(II) and chromone-2-carboxylic acid, a ligand from the group of hydroxypyrones, were synthesised according to the principles of green chemistry. The complexes were characterised by FT–IR and NMR spectroscopy, thermal and electrochemical analysis, and their structures are proposed. The results show the formation of mononuclear (1) and dinuclear hydroxo-bridged dinuclear copper(II) complexes (2 and 3). The results of cyclic voltammetry show that the copper in all complexes is in the +2-oxidation state. The antiproliferative activity was determined by MTT assay on 2D cell models in vitro on seven cell lines. The activity spectrum of complexes 1–3 ranged from the highest to the lowest value in the tumour cell lines tested, in the following order: Hep G2 > NCI-H358 > HT-29 > KATO III > MDA-MB 231 > Caco-2. The most effective concentration was 10⁻⁵ mol dm⁻³, which suppressed the growth of Hep G2 cells as follows: 69.5% (1), 64.8% (2) and 64% (3). The calculated selectivity index clearly shows that Hep G2 is the most sensitive cell line to copper complexes (SI = 1.623 (1); 1.557 (2), 1.431 (3). Full article

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver condition with potential progression to cirrhosis and impaired regeneration post-resection. A key mechanism underlying lipotoxicity is endoplasmic reticulum (ER) stress, particularly the activation of the unfolded protein response (UPR). This study investigates the interplay between lipid accumulation, endoplasmic reticulum (ER) stress, and cellular outcomes, focusing on the balance between autophagy and apoptosis. We cultured primary human hepatocytes (PHH) in a free fatty acid (FFA)-enriched medium for 120 h, assessing lipid accumulation, metabolism, and the expression of selected UPR markers. Additionally, we investigated the effects of lipid load on cell activity and growth in proliferating HepG2 cells. We observed that FFA uptake consistently induced ER stress, shifting cellular responses toward apoptosis under high lipid loads. Donor-specific differences were evident, particularly in lipid storage, excretion, and sensitivity to lipotoxicity. Some donors exhibited limited triglyceride (TAG) storage and excretion, leading to an excess of FFA whose metabolic fate remains unclear. Proliferation was more sensitive to lipid accumulation than overall cell activity, with even low FFA concentrations impairing growth, highlighting the vulnerability of regenerative processes to steatosis. The study elucidates how ER stress pathways, such as PERK-CHOP and IRE1α-JNK, are differentially activated in response to lipid overload, tipping the balance toward apoptosis in severe cases. The limited activation of repair mechanisms, such as autophagy, further emphasizes the critical role of ER stress in determining hepatocyte fate. The donor-dependent variability highlights the need for personalized strategies to mitigate lipotoxic effects and enhance liver regeneration in steatosis-related conditions. Full article

Background: This study encapsulates an in-depth correlation analysis for the biological activities (cytotoxicity, antimicrobial, and α-amylase inhibition) vs. the phytochemical classes (flavonoids “FV” and alkaloid “AL”) present in fenugreek seed extract. Methodology: Cell cultures for different cell lines were used to assess the cytotoxicity and selectivity (IC₅₀ value), agar diffusion assay was used to determine the MIC and MBC for different bacteria and fungi, whereas α-amylase inhibition was studied to evaluate the antidiabetic potential for the forty-five different origins of fenugreek seed extracts. An in-house analysis for the phytochemical classes of flavonoids (rutin, RT; quercetin, QT; luteolin, LT; kaempferol, KF) and alkaloid (trigonelline, TG) was performed for the seed extracts. Results: A lower IC₅₀ value (14.7 ± 1.46 µg/mL) was recorded for the IR3M extract against the HT29, MCF7 (13.03 ± 1.95 µg/mL), and MRC5 (14.58 ± 2.92 µg/mL) cell line. The extract with the lower IC₅₀ value (8.17 ± 0.73 µg/mL) against HepG2 was IR2M. For the antimicrobial activity, a lower MIC value (6.3 mg/mL) was observed for E2C, E2M, E3C, and I3H extracts against SF and for the E1M, Y3C, IR2H, IR3H, and IR3C extracts against SA. The lowest MBC value (12.5 mg/mL) was seen for E2C, E2M, E3C, and I3H against SF as well as for the extracts E1M, Y3C, IR2H, IR3H, and IR3C against SA. The extracts of Q1H (49.07 ± 2.45 µg/mL) and Y3C (43.65 ± 2.97 µg/mL) exhibited IC₅₀ values comparable to the standard drugs tested for α-amylase inhibition. The statistical models were of Pearson’s correlation. Principal component analysis (PCA) and a paired t-test established a strong positive correlation for the FV (QT, KF, LT) and alkaloid (TG) (p < 0.05) in the biological activities (cytotoxicity, antimicrobial, and α-amylase inhibition), thereby suggesting a substantial role for these phytochemical classes in the traditional and medicinal uses of fenugreek seeds. Conclusions: The FV and alkaloid are the key to impart the biological properties to the fenugreek seeds, hence their presence is utmost in the fenugreek seeds. This research work may be used as marker to help authenticate the fenugreek seeds for the quality variation in the major phytochemical classes. Full article

Kadsura coccinea is a traditional Chinese medicine whose roots have long been used to treat various ailments, but little is known about the efficacy of its leaves. In this study, the antidiabetic activity of K. coccinea leaf extract (KCLE) was determined, the main components of KCLE were identified using UPLC-TOF-MS, and network pharmacology and molecular docking were integrated to elucidate the antidiabetic mechanism of KCLE. The results showed that KCLE effectively increased the glucose consumption of IR-HepG2 cells through pyruvate kinase (PK) and hexokinase (HK), promoted glycogen synthesis, and inhibited α-glucosidase and α-amylase activities. KCLE also improves diabetes by regulating AKT1, TNF, EGFR, and GSK3β. These targets (especially AKT1 and TNF) have a high binding affinity with the main active ingredients of KCLE (rutin, luteolin, demethylwedelolactone, maritimetin, and polydatin). Pathway enrichment analysis showed that the antidiabetic effect of KCLE was closely related to the PI3K-Akt signaling pathway, MAPK signaling pathway, AGE-RAGE signaling pathway, and FoxO signaling pathway. These findings provide a theoretical basis for promoting the pharmacodynamic development of K. coccinea and its application in treating diabetes. Full article

Insulin resistance (IR) disrupts hepatic glucose metabolism and mitochondrial function, which contributes to metabolic disorders. The present study examined the effects of tomatine on glucose metabolism in high-glucose-induced IR hepatocytes and explored its underlying mechanisms using AML12 and HepG2 cell models. The results showed that tomatine did not exhibit cytotoxic effects. Under IR conditions, tomatine dose-dependently improved glucose metabolism by enhancing glucose consumption and restoring the mRNA expression of the glucose transporter Glut2 and gluconeogenesis-related genes (Pepck and G6pase). Mechanistically, tomatine activated the phosphorylation of AMP-activated protein kinase (AMPK) and upregulated the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), reversing the IR-induced suppression of the AMPK/PGC1α pathway. In addition, tomatine enhanced mitochondrial oxidative function by restoring the oxygen consumption rate, increasing ATP production, and upregulating mitochondrial oxidative phosphorylation complex proteins. Both genetic and pharmacological inhibition of AMPK abolished these beneficial effects, confirming its central role in mediating tomatine’s actions. Overall, our findings suggest that tomatine is a promising therapeutic candidate for enhancing hepatic glucose metabolism and mitochondrial function in IR-associated metabolic disorders through AMPK activation. Full article

Coriander (Coriandrum sativum) is a classical medicinal and edible herb as well as a spice, but the physicochemical and biological properties of its polysaccharides have not been fully studied. In this study, the polysaccharides were extracted using an ultrasonic-assisted method and purified from fresh coriander, and then the coriander polysaccharide (CSP) fraction was separated using an agarose gel Q-Sepharose Fast Flow column. The total sugar content, protein content and monosaccharides composition of CSPs were determined using a phenol–sulfuric acid method, Coomassie Brilliant Blue method and HPLC. The structural characterization was detected using ultraviolet spectrophotometry and FT-IR spectroscopy. DPPH and ABTS free radicals were used to explore their antioxidant activities, while the inhibitory abilities of α-amylase and α-glucosidase were used to evaluate their hypoglycemic activity. After that, the immunomodulatory and antitumor activities were investigated using macrophage RAW264.7 and HepG2 cells as the targets. The results showed that the total sugar and protein contents of CSPs were 66.90 ± 1.44% and 1.06 ± 0.32%, respectively. CSPs were mainly composed of fucose, rhamnose, arabinose, galactose, glucose, galacturonic acid and glucuronic acid, with a molar ratio of 1.13:15.11:9.60:25.98:1.55:44.33:2.29, and may be an acidic heteropolysaccharide containing pyran rings, α- and β-glycosidic bonds and glucuronic acid. Results from in vitro experiments of biological activities showed that the IC₅₀ of CSPs for scavenging DPPH and ABTS free radicals were 0.759 mg/mL and 1.758 mg/mL, respectively; the IC₅₀ values for inhibiting the activities of α-amylase and α-glucosidase were 0.634 mg/mL and 2.178 mg/mL, respectively; the CSPs with a concentration of 25~200 μg/mL showed no obvious toxicity to macrophage RAW264.7, and when treated with 100 μg/mL of CSPs, the relative cell phagocytosis capacity and secreted nitric oxide amount of RAW264.7 were 153.75 ± 12.01% and 133.56 ± 5.37%, respectively; CSPs showed a concentration-dependent ability to inhibit the growth of HepG2 cells within the test concentration of 0.25–2.0 mg/mL. Summarizing the results, due to their excellent antioxidant, immunomodulatory and anti-tumor activities, the coriander acid polysaccharides were expected to show good potential in comprehensive development of food and medicine. Full article