Agrimoniin

Exploring the Mechanisms of Traditional Chinese Herbal Therapy in Gastric Cancer: A Comprehensive Network Pharmacology Study of the Tiao-Yuan-Tong-Wei decoction.[Pubmed:38675376]

Pharmaceuticals (Basel). 2024 Mar 25;17(4):414.

The use of herbal medicine as an adjuvant therapy in the management of gastric cancer has yielded encouraging outcomes, notably in enhancing overall survival rates and extending periods of disease remission. Additionally, herbal medicines have demonstrated potential anti-metastatic effects in gastric cancer. Despite these promising findings, there remains a significant gap in our understanding regarding the precise pharmacological mechanisms, the identification of specific herbal compounds, and their safety and efficacy profiles in the context of gastric cancer therapy. In addressing this knowledge deficit, the present study proposes a comprehensive exploratory analysis of the Tiao-Yuan-Tong-Wei decoction (TYTW), utilizing an integrative approach combining system pharmacology and molecular docking techniques. This investigation aims to elucidate the pharmacological actions of TYTW in gastric pathologies. It is hypothesized that the therapeutic efficacy of TYTW in counteracting gastric diseases stems from its ability to modulate key signaling pathways, thereby influencing PIK3CA activity and exerting anti-inflammatory effects. This modulation is observed predominantly in pathways such as PI3K/AKT, MAPK, and those directly associated with gastric cancer. Furthermore, the study explores how TYTW's metabolites (Agrimoniin, baicalin, corosolic acid, and luteolin) interact with molecular targets like AKT1, CASP3, ESR1, IL6, PIK3CA, and PTGS2, and their subsequent impact on these critical pathways and biological processes. Therefore, this study represents preliminary research on the anticancer molecular mechanism of TYTW by performing network pharmacology and providing theoretical evidence for further experimental investigations.

The anti-colorectal cancer effect and metabolites of Agrimonia pilosa Ledeb.[Pubmed:38604512]

J Ethnopharmacol. 2024 Apr 9;329:118146.

ETHNOPHARMACOLOGICAL RELEVANCE: Agrimonia pilosa Ledeb. (Rosaceae, A. pilosa) has been used in traditional medicine in China, Japan, Korea, and other Asian countries for treatment of acute and chronic enteritis and diarrhea. Secondary metabolites have been isolated and tested for biological activities. It remains unclear in terms of its potential components of anti-colorectal cancer properties. AIM OF THE STUDY: The study aimed to how extracts from A. pilosa and their components influenced tumor microenvironment and the colorectal tumor growth in vivo on AOM/DSS induced colorectal cancer mice, the metabolites of A. pilosa was also been studied. MATERIALS AND METHODS: Different methods have been used to extract different parts of A. pilosa. And the anti-proliferation effect of these extracts on colon cancer cells have been tested. The components of A. pilosa and its metabolites in vivo were analyzed by UPLC-QTOF-MS/MS. The anti-colorectal cancer (CRC) effects of A. pilosa and its components in vivo were studied on AOM/DSS induced CRC mice. The effects of constituents of A. pilosa on the composition of immune cells in tumor microenvironment (TME) were analyzed by flow cytometry. 16 S rDNA technology was used to analyze the effect of administration on the composition of intestinal microflora. Pathological section staining was used to compare the morphological changes and molecular expression of intestinal tissue in different groups. RESULTS: The constituent exists in root of A. pilosa showed the strongest anti-proliferation ability on colon cancer cells in vitro. The extract from the root of A. pilosa could attenuate the occurrence of colorectal tumors induced by AOM/DSS in a concentration-dependent manner. Administration of the extract from the root of A. pilosa could affect the proportion of gammadeltaT cells, tumor associated macrophages and myeloid derived suppressor cells in TME, increasing the proportion of anti-tumor immune cells and decrease the immunosuppressive cells in the TME to promote the anti-tumor immune response. The administration of the extract adjusted the composition of gut microbiota and its components Agrimoniin and Agrimonolide-6-o-glucoside showed the strongest anti-CRC effect in vivo with adjusting the gut microbiota differently. CONCLUSIONS: The extract from root of A. pilosa showed anti-colorectal cancer effects in vivo and in vitro, affecting the composition of gut microbiota and the anti-tumor immune response. Within all components of A. pilosa, Agrimoniin and Agrimonolide-6-o-glucoside showed remarkable anti-CRC efficiency in vivo and in vitro. Besides, the metabolites of extract from root of A. pilosa in gastrointestinal tract mainly composed of two parts: Agrimonolide-related metabolites and Urolithins. The extract from root of A. pilosa could contribute to potential drugs for assisting clinical anti-colon cancer therapy.

Optimized Single-Step Recovery of Lipophilic and Hydrophilic Compounds from Raspberry, Strawberry and Blackberry Pomaces Using a Simultaneous Ultrasound-Enzyme-Assisted Extraction (UEAE).[Pubmed:37891873]

Antioxidants (Basel). 2023 Sep 22;12(10):1793.

An ultrasound-enzyme-assisted extraction (UEAE) was optimized to extract, simultaneously, the hydrophilic and lipophilic compounds from three berry pomaces (raspberry, strawberry and blackberry). First, an enzyme screening designated a thermostable alkaline protease as the most suitable enzyme to recover, in an aqueous medium, the highest yields of polyphenols and oil in the most efficient way. Secondly, the selected enzyme was coupled to ultrasounds (US) in sequential and simultaneous combinations. The simultaneous US-alkaline enzyme combination was selected as a one-single-step process and was then optimized by definitive screening design (DSD). The optimized parameters were: US amplitude, 20% (raspberry pomace) or 70% (strawberry and blackberry pomaces); pH, 8; E/S ratio, 1% (w/w); S/L ratio, 6% (w/v); extraction time, 30 min; temperature, 60 degrees C. Compared to conventional extractions using organic solvents, the UEAE extracted all the polyphenols, with around 75% of the active polyphenols (measured by the DPPH(●) method) and up to 75% of the initial oil from the berry pomaces. Characterized lipophilic compounds were rich in polyunsaturated fatty acids (PUFAs), tocols and phytosterols. The polyphenolics were analyzed by UPLC-MS/MS; characteristic ellagitannins of the Rosaceae family (sanguiin H-6 or Agrimoniin, sanguiin H-10, ...) and ellagic acid conjugates were found as the major components.

Kinetic Ultrasound-Assisted Extraction as a Sustainable Approach for the Recovery of Phenolics Accumulated through UVA Treatment in Strawberry By-Products.[Pubmed:37627988]

Foods. 2023 Aug 8;12(16):2989.

Ultrasound-assisted extraction (UAE) is an efficient and sustainable method for extracting bioactive compounds from agro-industrial by-products. Moreover, it has been reported that ultraviolet A (UVA) radiation can induce the biosynthesis and accumulation of bioactive phenolic compounds. This study optimized the efficiency of ultrasound-assisted extraction (UAE) for recovering ultraviolet A (UVA)-induced phenolic compounds in strawberry by-products (RF-N). The impact of three factors (solid-liquid ratio, ethanol concentration, and ultrasound power) on total phenolic compound (TPC) kinetics using Peleg's model was investigated. The developed model showed a suitable fit for both RF-N and strawberry by-products treated with UVA (RF-E). The optimal UAE conditions obtained were of a 1:30 ratio, 46% ethanol, and 100% ultrasound power, resulting in an average yield of 13 g total phenolics kg(-1). The bioaccessibility of phenolic compounds during in-vitro digestion was 36.5%, with Agrimoniin being the predominant compound. UAE combined with UVA treatment increased the bioactivity of RF extracts, displaying significant anti-proliferative effects on HT29 and Caco-2 cancer cell lines, as well as anti-inflammatory potential and cellular antioxidant activity. The ultrasound proved to be a sustainable and effective technique for extracting phenolic compounds from RF, contributing to the valorization of strawberry agro-industrial by-products, and maximizing their nutraceutical potential.

Agrimoniin is a dual inhibitor of AKT and ERK pathways that inhibit pancreatic cancer cell proliferation.[Pubmed:37156642]

Phytother Res. 2023 Sep;37(9):4076-4091.

Molecular-targeted therapy has shown its effectiveness in pancreatic cancer, while single-targeted drug often cannot provide long-term benefit because of drug resistance. Fortunately, multitarget combination therapy can reverse drug resistance and achieve better efficacy. The typical treatment characteristics of traditional Chinese medicine monomer on tumor are multiple targets, with small side effects, low toxicity, and so forth. Agrimoniin has been reported to be effective on some cancers, while the mechanism still needs to be clarified. In this study, we used 5-ethynyl-2'-deoxyuridine, cell counting kit-8, flow cytometry, and western blot experiments to confirm that Agrimoniin can significantly inhibit the proliferation of pancreatic cancer cell PANC-1 by inducing apoptosis and cell cycle arrest. In addition, by using SC79, LY294002 (the agonist or inhibitor of AKT pathway), and U0126 (the inhibitor of ERK pathway), we found that Agrimoniin inhibited cell proliferation by simultaneously inhibiting AKT and ERK pathways. Moreover, Agrimoniin could significantly increase the inhibitory effect of LY294002 and U0126 on pancreatic cancer cells. Meanwhile, in vivo experiments also supported the above results. In general, Agrimoniin is a double-target inhibitor of AKT and ERK pathways in pancreatic cancer cells; it is expected to be used as a resistance reversal agent of targeted drugs or a synergistic drug of the inhibitor of AKT pathway or ERK pathway.

Phytochemical Profiling of Extracts from Rare Potentilla Species and Evaluation of Their Anticancer Potential.[Pubmed:36902263]

Int J Mol Sci. 2023 Mar 2;24(5):4836.

Despite the common use of Potentilla L. species (Rosaceae) as herbal medicines, a number of species still remain unexplored. Thus, the present study is a continuation of a study evaluating the phytochemical and biological profiles of aqueous acetone extracts from selected Potentilla species. Altogether, 10 aqueous acetone extracts were obtained from the aerial parts of P. aurea (PAU7), P. erecta (PER7), P. hyparctica (PHY7), P. megalantha (PME7), P. nepalensis (PNE7), P. pensylvanica (PPE7), P. pulcherrima (PPU7), P. rigoi (PRI7), and P. thuringiaca (PTH7), leaves of P. fruticosa (PFR7), as well as from the underground parts of P. alba (PAL7r) and P. erecta (PER7r). The phytochemical evaluation consisted of selected colourimetric methods, including total phenolic (TPC), tannin (TTC), proanthocyanidin (TPrC), phenolic acid (TPAC), and flavonoid (TFC) contents, as well as determination of the qualitative secondary metabolite composition by the employment of LC-HRMS (liquid chromatography-high-resolution mass spectrometry) analysis. The biological assessment included an evaluation of the cytotoxicity and antiproliferative properties of the extracts against human colon epithelial cell line CCD841 CoN and human colon adenocarcinoma cell line LS180. The highest TPC, TTC, and TPAC were found in PER7r (326.28 and 269.79 mg gallic acid equivalents (GAE)/g extract and 263.54 mg caffeic acid equivalents (CAE)/g extract, respectively). The highest TPrC was found in PAL7r (72.63 mg catechin equivalents (CE)/g extract), and the highest TFC was found in PHY7 (113.29 mg rutin equivalents (RE)/g extract). The LC-HRMS analysis showed the presence of a total of 198 compounds, including Agrimoniin, pedunculagin, astragalin, ellagic acid, and tiliroside. An examination of the anticancer properties revealed the highest decrease in colon cancer cell viability in response to PAL7r (IC(50) = 82 microg/mL), while the strongest antiproliferative effect was observed in LS180 treated with PFR7 (IC(50) = 50 microg/mL) and PAL7r (IC(50) = 52 microg/mL). An LDH (lactate dehydrogenase) assay revealed that most of the extracts were not cytotoxic against colon epithelial cells. At the same time, the tested extracts for the whole range of concentrations damaged the membranes of colon cancer cells. The highest cytotoxicity was observed for PAL7r, which in concentrations from 25 to 250 microg/mL increased LDH levels by 145.7% and 479.0%, respectively. The previously and currently obtained results indicated that some aqueous acetone extracts from Potentilla species have anticancer potential and thus encourage further studies in order to develop a new efficient and safe therapeutic strategy for people who have been threatened by or suffered from colon cancer.

Adding value to strawberry agro-industrial by-products through ultraviolet A-induced biofortification of antioxidant and anti-inflammatory phenolic compounds.[Pubmed:36570174]

Front Nutr. 2022 Dec 7;9:1080147.

BACKGROUND: The revalorization of agro-industrial by-products by applying ultraviolet A (UVA) radiation to biofortify with phenolic compounds has been studied in recent times, showing improvements in the individual and total phenolic content and their bioactivity. Therefore, the main aim of this work was to optimize the biofortification process of phenolic compounds by UVA radiation to strawberry agro-industrial by-products (RF). Moreover, the effect of UVA radiation on the potential biological activity of the phenolics accumulated in RF due to the treatment was also determined. METHODS: The assays followed a factorial design with three variables at three levels: UVA dose (LOW, MEDIUM, and HIGH), storage temperature (5, 10, and 15 degrees C), and storage time (0, 24, 48, and 72 h). At each experimental condition, phenylalanine ammonia-lyase (PAL) and polyphenol oxidase (PPO) enzymatic activities, total phenolic compound content (TPC), phenolics profile (TPC(HPLC)), and Agrimoniin content (AGN) were evaluated; and the optimal UVA dose, storage time, and temperature were determined. In vitro bioaccessibility of the accumulated phenolic compound was studied on RF tissue treated with UVA at optimal process conditions. The digested extracts were tested for antiproliferative activity in colorectal cancer cells, cellular antioxidant capacity, and anti-inflammatory activity. RESULTS: The results showed that applying UVA-HIGH (86.4 KJ/m(2)) treatment and storing the tissue for 46 h at 15 degrees C increased PAL activity (260%), phenolic content (240%), and AGN (300%). The biofortification process improves the bioaccessibility of the main phenolic compound of RF by 9.8 to 25%. The digested optimum extract showed an IC50 for HT29 and Caco-2 cells of 2.73 and 5.43 mug/mL, respectively, and presented 60% cellular antioxidant capacity and 30% inhibition of NOX production. CONCLUSION: The RF treated with UVA is an excellent source of phenolic compounds; specifically, ellagitannins and the UVA radiation proved to be efficient in biofortify RF, significantly improving the phenolic compounds content and their bioactive properties with adequate bioaccessibility, adding value to the strawberry agro-industrial by-products.

Anticancer potential of acetone extracts from selected Potentilla species against human colorectal cancer cells.[Pubmed:36249795]

Front Pharmacol. 2022 Sep 29;13:1027315.

Cinquefoils have been widely used in local folk medicine in Europe and Asia to manage various gastrointestinal inflammations and/or infections, certain forms of cancer, thyroid gland disorders, and wound healing. In the present paper, acetone extracts from aerial parts of selected Potentilla species, namely P. alba (PAL7), P. argentea (PAR7), P. grandiflora (PGR7), P. norvegica (PN7), P. recta (PRE7), and the closely related Drymocalis rupestris (syn. P. rupestris) (PRU7), were analysed for their cytotoxicity and antiproliferative activities against human colon adenocarcinoma cell line LS180 and human colon epithelial cell line CCD841 CoN. Moreover, quantitative assessments of the total polyphenolic (TPC), total tannin (TTC), total proanthocyanidins (TPrC), total flavonoid (TFC), and total phenolic acid (TPAC) were conducted. The analysis of secondary metabolite composition was carried out by LC-PDA-HRMS. The highest TPC and TTC were found in PAR7 (339.72 and 246.92 mg gallic acid equivalents (GAE)/g extract, respectively) and PN7 (332.11 and 252.3 mg GAE/g extract, respectively). The highest TPrC, TFC, and TPAC levels were found for PAL7 (21.28 mg catechin equivalents (CAT)/g extract, 71.85 mg rutin equivalents (RE)/g extract, and 124.18 mg caffeic acid equivalents (CAE)/g extract, respectively). LC-PDA-HRMS analysis revealed the presence of 83 compounds, including brevifolincarboxylic acid, ellagic acid, pedunculagin, Agrimoniin, chlorogenic acid, astragalin, and tiliroside. Moreover, the presence of tri-coumaroyl spermidine was demonstrated for the first time in the genus Potentilla. Results of the MTT assay revealed that all tested extracts decreased the viability of both cell lines; however, a markedly stronger effect was observed in the colon cancer cells. The highest selectivity was demonstrated by PAR7, which effectively inhibited the metabolic activity of LS180 cells (IC(50) = 38 mug/ml), while at the same time causing the lowest unwanted effects in CCD841 CoN cells (IC(50) = 1,134 mug/ml). BrdU assay revealed a significant decrease in DNA synthesis in both examined cell lines in response to all investigated extracts. It should be emphasized that the tested extracts had a stronger effect on colon cancer cells than normal colon cells, and the most significant antiproliferative properties were observed in the case of PAR7 (IC(50) LS180 = 174 mug/ml) and PN7 (IC(50) LS180 = 169 mug/ml). The results of LDH assay revealed that all tested extracts were not cytotoxic against normal colon epithelial cells, whereas in the cancer cells, all compounds significantly damaged cell membranes, and the observed effect was dose-dependent. The highest cytotoxicity was observed in LS180 cells in response to PAR7, which, in concentrations ranging from 25 to 250 mug/ml, increased LDH release by 110%-1,062%, respectively. Performed studies have revealed that all Potentilla species may be useful sources for anti-colorectal cancer agents; however, additional research is required to prove this definitively.

Agrimonia eupatoria L.: An integrative perspective on ethnomedicinal use, phenolic composition and pharmacological activity.[Pubmed:35752261]

J Ethnopharmacol. 2022 Oct 5;296:115498.

ETHNOPHARMACOLOGICAL RELEVANCE: Agrimonia eupatoria L., a plant which belongs to the Rosaceae family, is widespread in temperate regions, particularly throughout the northern hemisphere. In folk medicine, this plant species has been used for its astringent, anti-inflammatory, analgesic and hypotensive properties as well as in gastrointestinal disorders. As these biological properties have been linked to its phenolic composition, this plant species could be an interesting source of bioactive compounds with therapeutic potential. AIM OF THE STUDY: The aim of the present review is to provide a comprehensive overview of the scientific literature on A. eupatoria, particularly in regard to its ethnobotanics and ethnomedicinal uses, phenolic composition and biological and pharmacological activities. MATERIAL AND METHODS: Literature was retrieved from several bibliographic sources, namely PubMed, ScienceDirect and Google Scholar, since the first report on A. eupatoria in 1993. RESULTS: Regarding the phytochemical composition, A. eupatoria is rich in phenolic acids, flavonoids and tannins. The most commonly reported compounds are astragalin, cynaroside, hyperoside, isoquercitrin, isovitexin, rutin, catechin, procyanidin B3 and Agrimoniin. In terms of bioactivity, extracts or fractions obtained from this plant species have shown antioxidant, antimicrobial, antidiabetic, antinociceptive and anti-inflammatory properties, among others. So far, two clinical studies with the infusion of A. eupatoria have shown hepatoprotective properties as well as a protective role in cardiovascular disease, metabolic disorders and diabetes. CONCLUSIONS: In this review, an integrative perspective on ethnomedicinal use, phenolic composition and pharmacological activity of A. eupatoria has been provided. As can be seen, this plant species exhibits several potential applications, including those beyond its traditional ethnomedicinal uses, as the safety of its consumption has been shown clinically. There still is limited pharmacological evidence that corroborates the ethnomedicinal uses of this plant species as well as regarding the specific bioactive compounds.

New Properties and Mitochondrial Targets of Polyphenol Agrimoniin as a Natural Anticancer and Preventive Agent.[Pubmed:34959369]

Pharmaceutics. 2021 Dec 5;13(12):2089.

Agrimoniin is a polyphenol from the group of tannins with antioxidant and anticancer activities. It is assumed that the anticancer action of Agrimoniin is associated with the activation of mitochondria-dependent apoptosis, but its mitochondrial targets have not been estimated. We examined the direct influence of Agrimoniin on different mitochondrial functions, including the induction of the mitochondrial permeability transition pore (MPTP) as the primary mechanism of mitochondria-dependent apoptosis. Agrimoniin was isolated from Agrimonia pilosa Ledeb by multistep purification. The content of Agrimoniin in the resulting substance reached 80%, as determined by NMR spectroscopy. The cytotoxic effect of purified Agrimoniin was confirmed on the cultures of K562 and HeLa cancer cells by the MTT assay. When tested on isolated rat liver mitochondria, Agrimoniin at a low concentration (10 microM) induced the low-amplitude swelling, which was inhibited by the MPTP inhibitors ADP and cyclosporine A, activated the opening of MPTP by calcium ions and stimulated the respiration supported by succinate oxidation. Also, Agrimoniin reduced the electron acceptor DCPIP in a concentration-dependent manner and chelated iron ions. Owing to all these properties, Agrimoniin can stimulate apoptosis or activate mitochondrial functions, which can be helpful in the prevention and elimination of stagnant pathological states.

The Aerial Parts of Agrimonia procera Wallr. and Agrimonia eupatoria L. as a Source of Polyphenols, and Especially Agrimoniin and Flavonoids.[Pubmed:34946788]

Molecules. 2021 Dec 20;26(24):7706.

Plants of the genus Agrimonia L. perfectly fit the current trends in nutrition and food technology, namely, the need for raw materials with a high content of bioactive natural compounds, including polyphenols, which could be added to food. The composition of polyphenolics, including Agrimoniin and flavonoids, in the aerial parts of Agrimonia procera Wallr. (A. procera) and Agrimonia eupatoria L. (A. eupatoria) (Rosaceae) was determined using HPLC-DAD-MS. The polyphenolic content of A. procera was found to be 3.9%, 3.2%, 2.9%, 1.8% and 1.1%, and that of A. eupatoria was determined to be 1.3%, 0.3%, 0.9%, 0.6% and 0.5% in the dry matter of leaves, stems, fruits, seeds and hypanthia, respectively. Except for A. procera hypanthia, Agrimoniin was the main polyphenolic compound in the aerial parts of the studied Agrimonia species. Both plants are also a valuable source of flavonoid glycosides, especially apigenin, luteolin and quercetin. The obtained data indicate that both A. procera and A. eupatoria are potentially good sources of polyphenols (albeit significantly different in terms of their qualitative and quantitative composition), and may not only be a medicinal raw material, but also a valuable material for food use such as nutraceuticals or functional food ingredients.

Agrimoniin inhibits the activity of CYP1A2, 2D6, and 3A4 in human liver microsomes.[Pubmed:34806927]

Xenobiotica. 2021 Dec;51(12):1360-1365.

The effect of Agrimoniin on the activity of cytochrome P450 (CYP450) enzymes would induce drug-drug interaction, which leads to adverse effects or even failure of therapy.Agrimoniin was incubated with the specific substrates of eight human liver CYP isoforms in pooled human liver microsomes. The enzyme kinetics and time-dependent study were performed to obtain kinetic parameters and characteristics in vitro.Agrimoniin significantly inhibited the activity of CYP1A2, 2D6, and 3A4 in a dose-dependent manner with IC(50) values of 6.26, 9.35, and 8.30 muM, respectively. Agrimoniin served as a non-competitive inhibitor of CYP3A4 and a competitive inhibitor of CYP1A2 and 2D6. Moreover, the incubation time also significantly affected the inhibition of CYP3A4.In vitro inhibitory effect of Agrimoniin on the activity of CYP1A2, 2A6, and 3A4 was reported in this study. The potential drug-drug interactions between Agrimoniin and drugs metabolised by CYP1A2, 2D6, and 3A4 should be paid special attention.

Agrimoniin sensitizes pancreatic cancer to apoptosis through ROS-mediated energy metabolism dysfunction.[Pubmed:34785107]

Phytomedicine. 2022 Feb;96:153807.

BACKGROUND: Pancreatic cancer is a fatal tumor, which is one of the most common malignant tumors at present. Patients with pancreatic cancer also respond poorly to chemotherapy or radiation therapy and may be accompanied by serious adverse reactions. Therefore, to find an effective way to inhibit the initiation and progression of pancreatic cancer is important to improve the survival and development of patients. Agrimoniin, a polyphenol compounds isolated from Agrimonia pilosa ledeb, has antiviral, antimicrobial, and anticancer activities in vivo and in vitro. However, its molecular mechanism in pancreatic cancer remains to be determined. PURPOSE: We aimed to investigate the effect of Agrimoniin in pancreatic cancer and its underlying mechanism in vivo and in vitro. METHODS: The proliferation was detected by colony formation, cell proliferation and toxicity, and real-time cell analysis techniques. The apoptosis was detected by flow cytometry and Western blot. Flow cytometry was used to measure the level of reactive oxygen species (ROS) and apoptosis. The level of intracellular ROS or mitochondrial membrane potential was measured with a DCFH-DA or JC-1 probe. Cell metabolism assays were analyzed and evaluated by using Agilent Seahorse Bioscience XF96 Extracellular Flux Analyzer. The target proteins were analyzed by Western blot. Subcutaneous cancer models in nude mice were established to evaluate the anticancer effects in vivo. RESULTS: Agrimoniin inhibited cell growth and promoted cell apoptosis by regulating cell metabolism in pancreatic cancer cells. Agrimoniin increased the ROS level in pancreatic cancer cells by suppressing Nrf2-dependent ROS scavenging system and disrupting normal mitochondrial membrane potential. We also found that Agrimoniin significantly disrupted mitochondrial function and reduced the protein expression of mTOR/HIF-1alpha pathway and subsequently decreased oxygen consumption rate and extracellular acidification rate. Eventually, Agrimoniin affected intracellular energy metabolism and induced apoptosis of pancreatic cancer cells. CONCLUSIONS: These findings reveal the novel function of Agrimoniin in promoting apoptosis of pancreatic cancer cells through mediating energy metabolism dysfunction. Altogether, the potential new targets and their synergies discovered in this research are of great significance for cancer treatment and drug development.

Strawberry agro-industrial by-products as a source of bioactive compounds: effect of cultivar on the phenolic profile and the antioxidant capacity.[Pubmed:38650292]

Bioresour Bioprocess. 2021 Jul 13;8(1):61.

The post-harvest processing of strawberries generates considerable amounts of by-products that consist of the inedible parts of the fruit (sepal, calyx, stem, and non-marketable portion of the fruit), which is an environmental problem for local producers and industries. This study aimed to revalue these kinds of tissues through identifying and quantifying the genotype influence on the total phenolic content, phenolic profile, and the antioxidant activity of the by-products from three strawberry cultivars: 'Festival' (FE), 'San Andreas ' (SA), and 'Camino Real' (CR). The total phenolic content was determined by the Folin-Ciocalteu method, in-vitro antioxidant activity by the DPPH* radical scavenging method and the phenolic profile by PAD-HPLC. The different genotypes showed significant differences (p < 0.05) in total phenolic content (TPC), FE being the one with the highest TPC (14.97 g of gallic acid equivalents < GAE > /Kg of by-product < R >), followed by SA and CR cultivars. The antioxidant capacity of the SA and FE tissues were similar (p > 0.05) and higher (15.1-16.3 mmol Trolox equivalents < TE > /Kg R) than CR. Eight main phenolic compounds were identified and quantified on the three cultivars. Agrimoniin was the principal polyphenol (0.38-1.56 g/Kg R), and the cultivar FE had the highest concentration. This compound showed the highest correlation coefficient with the antioxidant capacity (R(2) 0.87; p < 0.001). This study highlighted the impact of the multi-cultivar systems in strawberry production on the bioactive potential and the diversity of secondary metabolites obtained from strawberry agro-industrial by-products at a low cost.