Fibroblast Proliferation and Migration in Wound Healing by Phytochemicals: Evidence for a Novel Synergic Outcome

Addis, Roberta; Cruciani, Sara; Santaniello, Sara; Bellu, Emanuela; Sarais, Giorgia; Ventura, Carlo; Maioli, Margherita; Pintore, Giorgio Antonio Mario

doi:10.7150/ijms.43986

Cited by 110 publications

(71 citation statements)

References 57 publications

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“…Our results confirmed the relationship between antioxidant activity due to the presence of bioactive phenolic compounds and cell proliferation, as reported by other studies [ 59 , 60 ]. In particular, this study further highlights that a proactive use of waste to ameliorate regenerative and antioxidant processes can be associated with a wide range of final usage.…”

Section: Resultssupporting

confidence: 93%

Onion Peel: Turning a Food Waste into a Resource

et al. 2021

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Food waste is a serious problem for food processing industries, especially when it represents a loss of a valuable source of nutrients and phytochemicals. Increasing consumer demand for processed food poses the problem of minimizing waste by conversion into useful products. In this regard, onion (Allium cepa) waste consisting mainly of onion skin is rich in bioactive phenolic compounds. Here, we characterized the flavonoid profiles and biological activities of onion skin wastes of two traditional varieties with protected geographical indication (PGI), the red “Rossa di Tropea” and the coppery “Ramata di Montoro”, typically cultivated in a niche area in southern Italy. The phytochemical profiles of exhaustive extracts, characterized by ultra-high-performance liquid chromatography coupled with ultraviolet (UV) detection and high-resolution mass spectrometry, revealed that flavonols and anthocyanins were the characteristic metabolite classes of onion skins. Quercetin, quercetin glucosides and their dimer and trimer derivatives, and, among anthocyanins, cyanidin 3-glucoside, were the most abundant bioactive compounds. The potential of onion skins was evaluated by testing several biological activities: ABTS/oxygen radical absorbance capacity (ORAC) and in vitro alpha-glucosidase assays were performed to evaluate the antioxidant and anti-diabetic properties of the extracts and of their main compounds, respectively, and proliferative activity was evaluated by MTT assay on human fibroblasts. In the present study, by observing various biological properties of “Rossa di Tropea” and “Ramata di Montoro” onion-dried skins, we clearly indicated that this agricultural waste can provide bioactive molecules for multiple applications, from industrial to nutraceutical and cosmetical sectors.

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Section: Resultssupporting

confidence: 93%

Onion Peel: Turning a Food Waste into a Resource

et al. 2021

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“…About 14–25% of diabetic patients have the complication of foot ulcer. The fibroblast cells-based wound scratch assay is one of the inexpensive and well-recognized techniques to understand the wound-healing efficiency of natural products [ 41 ]. There are plenty of plant extracts playing an astonishing role in accelerating the healing process.…”

Section: Resultsmentioning

confidence: 99%

Ethyl Acetate Fraction of Helianthus tuberosus L. Induces Anti-Diabetic, and Wound-Healing Activities in Insulin-Resistant Human Liver Cancer and Mouse Fibroblast Cells

et al. 2021

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Traditional, complementary, and integrative medicine are globally accepted alternative methods for the treatment of diabetes mellitus (DM). However, the mechanism of anti-diabetic effects of Helianthus tuberosus L. remains unproven. In the present study, antioxidant and anti-diabetic activity of the tubers of H. tuberosus were studied in detail. Methanolic extracts of H. tuberosus tubers were subjected to solvent fractionation method by increasing the polarity of the solvent using n-hexane, and ethyl acetate. The obtained methanol extracts and its fractions were subjected to free radical scavenging activity (DPPH and ABTS assay) and in vitro enzyme (α-amylase and α-glucosidase) inhibition assay. Moreover, glucose uptake in insulin-resistant HepG2 cell line was analyzed. The preliminary phytochemical analysis confirmed the presence of phenolic and flavonoid compounds in the active fraction. The radical scavenging and in vitro diabetic related enzyme inhibitory activities were found to be dose dependent. The maximum ABTS+ and DPPH scavenging activity was documented in ethyl acetate fraction of the H. tuberosus followed by methanol extract, hexane fraction, and methanol fraction. We also found that H. tuberosus showed a less toxicity in mouse fibroblast cells and enhance the glucose uptake in insulin-resistant HepG2 cells. Besides, the ethyl acetate fraction of the H. tuberosus analyzed by UPLC-QTOF-MS-MS and GC/MS revealed the presence of phenolic compounds such as neochlorogenic acid, chlorogenic acid, caffeic acid, 5-O-(4-coumaroyl)-quinic acid, feruloylquinic acid, caffeoylquinic acid, isoxazolidine, salicylic acid β-D-glucoside, dicaffeoylquinic acid isomers, salvianolic acid derivative isomers, and 1,4 dicaffeoylquinic acid etc. Among the identified phytochemicals, six were chosen for molecular docking study to explore their its inhibitory interactions with α-amylase and α-glucosidase. Taken together, the findings of the present study suggested that phytocompounds of EAF were responsible for the significant in vitro antioxidant, wound-healing, and anti-diabetic activities.

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“…The authors also highlighted that the synergistic effects could target multiple levels of different pathways and emphasised on the synergy among pure compounds as a method of new drug discovery. More interestingly, a recent study by Addis et al 57 demonstrated the synergistic effect of waste extract from different medicinal plants in improving fibroblast proliferation and migration which otherwise had been reported to have inhibitory effect on cancer cell Figure 7. Graphical summary of the effects of BLE on methylglyoxal metabolism.…”

Section: Discussionmentioning

confidence: 97%

Evaluation of Anti-proliferative Effects of Barringtonia racemosa and Gallic Acid on Caco-2 Cells

Aziz

Junit

2020

Sci Rep

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Barringtonia racemosa leaf water extract (BLE) had been shown to have high gallic acid (GA) content and BLE has been postulated to have anti-proliferative effects towards colorectal cancer. This study aims to further investigate the mechanism underlying the anti-proliferative effect of BLE in Caco-2 cells and to determine if GA is responsible for the observed effects. Both BLE and GA inhibited Caco-2 cells in a dose-dependent manner. Cells exposed to IC 50 concentration of BLE and GA showed reduced antioxidant activities. GA-treated Caco-2 cells experienced higher oxidative stress compared to cells treated with BLE. Both BLE and GA significantly up-regulated the expression of SLC2A1. BLE but not GA, significantly down-regulated the expression of ADH4. Meanwhile, GA but not BLE, significantly up-regulated AKRIB10 and GLO1 but significantly down-regulated HAGH. Alterations in gene expression were coupled with changes in extracellular glucose and pyruvate levels. While BLE decreased intracellular pyruvate, GA did the opposite. Both intracellular and extracellular D-lactate were not affected by either BLE or GA. GA showed more pronounced effects on apoptosis while BLE irreversibly reduced cell percentage in the G0/G1 phase. In conclusion, this study demonstrates the multiple-actions of BLE against Caco-2 cells, potentially involving various polyphenolic compounds, including GA. Barringtonia racemosa (L.) Spreng is a medicinal plant belonging to the Lecythideceae family that is commonly found throughout Eastern Africa, Polynesia, Africa and Asia including Malaysia 1. In Malaysia, the shoot and young leaves of B. racemosa are usually consumed raw as a salad with various condiments, and different parts of the plant are used in traditional medicine 2. Studies on various parts of B. racemosa have demonstrated its biological activities that includes antibacterial 3 , antifungal 4 , antioxidant 5 , anti-inflammatory 6 and anti-cancer 7-9. Initial analysis performed by our group indicated that the leaf water extract of B. racemosa (BLE) had the highest polyphenolic and ascorbic acid content as well as antioxidant activities amongst various extracts prepared in solvents of different polarities, including water, ethanol, ethyl acetate and hexane 10. Ultra-high performance liquid chromatography (UHPLC) analyses of the BLE revealed the presence of gallic acid (GA), protocathechuic acid, ellagic acid, quercetin, kaempferol and rutin 10,11. The anti-proliferative activities of B. racemosa leaf extract was reported against cervical cancer cell line, HeLa 7 , tumour in mice challenged with Dalton's Lymphoma Ascitic cells 9 and leukemic cell lines, MOLT-3 and REH 8. A recent study conducted by our group found that BLE had a direct effect on the regulation of gene expression in HepG2 cells 12. Further in-silico analysis using Ingenuity Pathway Analysis (IPA) software revealed that the effect of BLE was associated to "cancer, cell death and survival and cell movement" and "cell cycle, connective tissue development and function, cellula...

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Fibroblast Proliferation and Migration in Wound Healing by Phytochemicals: Evidence for a Novel Synergic Outcome

Cited by 110 publications

References 57 publications

Onion Peel: Turning a Food Waste into a Resource

Onion Peel: Turning a Food Waste into a Resource

Ethyl Acetate Fraction of Helianthus tuberosus L. Induces Anti-Diabetic, and Wound-Healing Activities in Insulin-Resistant Human Liver Cancer and Mouse Fibroblast Cells

Evaluation of Anti-proliferative Effects of Barringtonia racemosa and Gallic Acid on Caco-2 Cells

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