Hesperidin from Orange Peel as a Promising Skincare Bioactive: An Overview
Abstract
:1. Introduction
2. Studies Published in The Last Decade—An Overview
2.1. Research Methodology
2.2. Results
3. Hesperidin Extraction and Purification from Oranges’ Peel Waste
4. Application of Hesperidin’s Biological Activities on Skincare
4.1. Antiaging and Skin’s Barrier Improvement
Hesperidin/ Extract Type | Hesperidin Levels Tested | Testing Model | Main Biological Properties | Formulation | Potential Applications | Molecular Pathways/ Other Relevant Properties | Ref. |
---|---|---|---|---|---|---|---|
Commercial hesperidin | ≈35–70% (w/v) | In vitro non-cellular assays | Radical scavenging activity increase in a dose-dependent manner. | Complex of hesperidin with modified silica (1:1, 1:2 or 2:1 (w/w)) | Cosmetics/ Cosmeceuticals | Complex’s antioxidant properties were higher than free hesperidin | [23] |
Rutaceae fruits extract | 1254.67 μg/mL | S. epidermidis E.coli P. acnes | Radical scavenging activity; Antibacterial activity against S. epidermidis, E. coli and P. acnes. | Mixed Rutaceae fruits hesperidin-rich ethanolic extract fermented with mushroom mycelium | Cosmetics/ Cosmeceuticals | N/A | [35] |
C. unshiu peel extract | 0.25–1% (w/v) | HDFs cells | MMP-1 expression decreases in a dose-dependent manner; Senescent cells decrease; Collagen biosynthesis increases. | C. unshiu peel extract fermented with S.commune | Cosmetics/ Cosmeceuticals | N/A | [44] |
Citrus sinensis peel bagasse | Corrosion tests: 100 µg/mL Collagenase assay: 0.08–0.9 mmol/L | FTS cells | Chelation activity; Collagenase inhibition; Antioxidant activity. | Nanoemulsion: hesperidin; glycerol; orange oil, poloxamer (Pluronic F127); and water. Nanoemulsion Silky Cream: BisPEG/PPG-16/16 PEG/PPG-16/16 dimethicone; caprylic/capric triglyceride (1%); muru muru butter (1%); cupuaçu butter (1%); andiroba oil (3%); GMS (2%); cetostearyl alcohol (3%); mineral oil (5%); carbopol ULTREZ 10 (0.2%); nano-emulsion (79.8%); triethanolamine (5 drops); vit E-acetate (0.05%); ethylhexylglicerin, phenoxy-ethanol (0.05%) | Cosmetics/ Cosmeceuticals | Modulation of MMPs activities | [63] |
Commercial hesperidin | 50 µM | HaCaT cells exposed to PM2.5 | Intracellular ROS levels reduction; Apoptotic index reduction; Protein carbonylation and intracellular vacuoles accumulation reversion; Reversion of elevated mitochondrial depolarization; Overall inhibitory effect on PM2.5-induced skin senescence and aging. | N/A | Cosmetics/ Cosmeceuticals | Cell viability restoration via PI3K/Akt activation; MAPK activation and autophagy/apoptosis-related protein expression mitigation; Increase in the anti-apoptotic protein Bcl-2 expression; Cell arrest in the G0/G1 phase decrease; β-galactosidase activity and MMP-associated senescence decrease; Oxidation effects decreased by c-Jun and c-Fos protein levels reduction | [80,81] |
Commercial hesperidin | 0.02% (w/v) | HaCaT cells | In vitro enhancement of antimicrobial peptide’s mRNA expression. | 0.02% hesperidin; 70% ethanol (w/v) | Cosmetics/ Cosmeceuticals | Increase in epidermal differentiation-related protein expression (loricrin and filaggrin); β-glucocerebrosidase and glutathione reductase activity regulation | [84,85] |
. | 1.03 mmol | In vitro non-cellular assays | Radical scavenging activity. | Hesperidin-conjugated pectins: pectin aqueous solution of 8 g (2.5 wt%); hesperidin intermediate (1.03 mmol) solution into a 7.5 wt% sodium hydroxide solution and epichlorohydrin (1.03 mmol) Hesperidin-conjugated pectins Hydrogels: pectin conjugates (5 wt% pectin solution) individually crosslinked with Ca2+, Zn2+, and Fe3+ (0.22 mM ionic solutions) | Cosmetics/ Cosmeceuticals | Hesperidin’s ion-binding ability induced the crosslinking of the hydrogel conjugates | [86] |
Commercial hesperidin | 0.05% (w/w) | In vitro non-cellular assays | Formulation’s bioadhesive properties improvement. | Biocomposites of cellulose, collagen, and hesperidin (4:1:0.05 (w/w)) | Cosmetics/ Cosmeceuticals | N/A | [87] |
4.2. UVA and UVB Radiation-Induced Skin Damage
4.3. Skin’s Hyperpigmentation and Depigmentation Conditions
4.4. Wound Healing
4.5. Skin Cancer and Other Cutaneous Diseases
Hesperidin/ Extract Type | Hesperidin Levels Tested | Testing Model | Main Biological Properties | Formulation | Potential Applications | Other Relevant Properties/ Molecular Pathways | Ref. |
---|---|---|---|---|---|---|---|
Sweet orange peel extract | 0.05–1 mg/mL | A. flavus A. parasiticus A. niger A. ochraceous F. proliferitum P. verrucosum BJ-1 cells Cancerous cell lines (HCT-116/MCF7/HepG2) | Liposome protection against UV-induced peroxidation; DNA protection activity; Free hesperidin presents pro-oxidant activity against cancerous cells; Antifungal activity; Growth inhibition of MCF-7 and HepG-2; NPs reduced cytotoxic effects against normal cells (BJ-1). | Nanoparticles (NPs): hesperidin (16.5 g) and PEG (50 g) | Skincare Pharmaceutical/ Therapeutic Agent | Hesperidin-loaded NPs enhanced protection capacity against DNA damage (maybe due to the alteration of the free hesperidin’s delivery, inside the cells, at the site of action) | [64] |
Commercial hesperidin | 10–50 μM | Epidermoid carcinoma cell line (A431 cells) | Decreasing in A431 viability and colony-forming potential in a dose-dependent manner; A high number of A431 cells in the S phase; Augmented ROS levels, increased cytosolic Ca2+ level, and reduced mitochondrial membrane potential level in A431; DNA breakage and non-apoptotic cell death inducing in A431. | N/A | Skincare Pharmaceutical/ Therapeutic Agent | Cyclin D, CDK2, and thymidylate synthase expression decreased in A431 cells; Reduced ATP levels by up to 40% in A431 cells | [73] |
Commercial hesperidin | In vivo (oral intake): 125–500 mg/Kg/day In vitro: 5–20 μg/mL | Mouse HaCaT cells | Reduced keratinocyte excessive proliferation and ameliorated abnormal differentiation of epidermal cells in in vitro psoriasis-like-induced model; Reduced the pathological changes of psoriasiform dermatitis by reducing localized inflammatory cytokine expression in vivo; Reduce excessive cell proliferation and differentiation in skin lesions in a dose-dependent manner in vivo. | N/A | Skincare Pharmaceutical/ Therapeutic Agent | Inhibition of tumor cell proliferation in a time/dosage-dependent manner; Hesperidin was found to be present in the stratum corneum and upper spinous layer after each dose | [115] |
Commercial hesperidin | Formulation’s oral intake: 100–400 mg/Kg/day | Swiss albino mice | Reducing of the tumor incidence in a dose-dependent manner; Reduced average number of tumors in a dose-dependent manner; Reduced neoplastic transformation in skin cells. | Hesperidin in saline water containing 0.5% (w/v) carboxymethyl-cellulose | Skincare Pharmaceutical/ Therapeutic Agent | Catalase and SOD activity enhancement in skin tumors after 24 weeks of treatment; GSH levels and activity increase in a dose-dependent manner; Reduction in the expression of Rassf7, Nrf2, PARP, and NF-κB genes in a dose-dependent manner; Inhibition of MDA in skin tumors, in a dose-dependent manner, leads to a lipid peroxidation decrease | [116] |
Commercial hesperidin | Oral intake: 0.1% (w/w) | Splenocytes from NC/Nga mice | No atopic dermatitis-induced skin lesions observed after treatment; Clinical scores (evaluation of atopic dermatitis symptoms) of hesperidin-fed mice increased until 10 weeks of age. | N/A | Skincare Pharmaceutical/ Therapeutic Agent | Increase in IgE serum levels; Decrease in IFN-c, IL-17 and IL-10 levels | [118] |
Hesperidin from micronized purified flavonoid fraction | Oral intake: 50 mg | Human 45-year-old male (case report) | Treatment improved the patient pigmented purpuric dermatoses lesions, after 2 weeks. | Oral intake: diosmin (450 mg), hesperidin (50 mg), E. prostata extract (100 mg), and calcium dobesilate (500 mg) | Skincare Pharmaceutical/ Therapeutic Agent | Surface expression of monocyte or neutrophil CD62L reduction; Leukocyte activation inhibition; VEGF expression downregulation; Decreasing of TNF-α, MMPs and NGAL expression; Production of oxygen free radical and lipid peroxidation inhibition | [119] |
Hesperidin from orange waste | 5–45 μmol/L | A375 cells CHL01 cells SKMEL147 cells | DPPH scavenging activity; No cytotoxicity to all cell lines at the tested concentrations. | Nanostructured lipid carriers: cupuaçu butter mixed with buriti oil, anhydrous lanolin (10% v/v), and L-hesperidin (4 mmol) | Skincare Pharmaceutical/ Therapeutic Agent | N/A | [121] |
5. Concluding Remarks
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Hesperidin/ Extract Type | Hesperidin Levels Tested | Testing Model | Main Biological Properties | Formulation | Potential Applications | Molecular Pathways/ Other Relevant Properties | Ref. |
---|---|---|---|---|---|---|---|
Commercial hesperidin | 0.0125–1 mM | HaCaT cells | ROS scavenging activity increases in a dose-dependent manner; UVB absorption activity; DNA protection against UVB; Optimal hesperidin concentration: 50 μM. | N/A | Cosmetics/ Cosmeceuticals | Mitochondrial membrane depolarization regulation by apoptotic pathways inhibition; Caspase-3, caspase-9, and BAX downregulation; Upregulated expression of Bcl-2; Prevention of protein oxidation against UVB-induced ROS | [75] |
Commercial hesperidin | 10–320 μg/mL | HaCaT cells | Cell viability increases in a concentration-dependent manner; Cell growth enhancement after inhibition by UVA; Enhancement of SOD activity; Reduction in ROS. | N/A | Cosmetics/ Cosmeceuticals | Reduction in MDA content; Downregulation of TNF-α mRNA/ protein, IL-1β mRNA/protein, and IL-6 mRNA/protein expression; Increase in T-AOC levels; Potential as a sunscreen agent | [88] |
Commercial hesperidin | 5–20 μM | HEKs cells HDFs cells | In vitro inhibition of UVB-induced angiogenesis. | N/A | Cosmetics/ Cosmeceuticals | Repression of MMP-9, MMP-13, and VEGF expression; Regulation of MEK/ERK and PI3K/Akt pathways | [89] |
Hesperidin from Citrus unshiu | 20 µg/mL | HaCaT cells | Regulation of inflammatory response. | N/A | Cosmetics/ Cosmeceuticals | Downregulation of IL-8 and TNF-α mRNA/protein expression; Inhibition of NF-ƙB/IƙBα signal cascade; Inhibition of p38 MAPK phosphorylation; Inhibition of COX-2 activation | [90] |
Commercial hesperidin | 0.3% (w/v) | In vitro non-cellular assays | Inhibition of short-life radicals; Inhibition of ABTS radical; Absorption of 99% UVB radiation and 83% UVA radiation. | NLCs: amaranth oil; pumpkin seed oil; 7% UVA filter; diethylamino hydroxybenzoyl hexyl benzoate; 7% UVB filter; ethylhexyl salicylate; and 3% hesperidin. NLCs-Carbol gel (ratio 1:1) cosmetic formulation: final composition of 3.17% diethylamino-hydroxybenzoyl hexyl benzoate, 3.17% ethylhexyl salicylate; and 1.13% hesperidin | Cosmetics/ Cosmeceuticals | In vitro, hesperidin presented a burst pattern with an accelerated release from the NLCs | [91] |
Citrus sinesis L. peel extract | 500–1000 mg of extract | In vitro non-cellular assays | In vitro inhibition activities of DPPH radical, elastase and collagenase. | NLCs optimal formulation: cocoa butter/olive oil and 1000 mg extract Extract-NLCs cream: clove (Eugenia caryophyllus), nagarmotha (Cyperus scariosus), tulsi (Ocimum sanctum), nutmeg (Myristica fragrans), linseed (Linum usitatissium), wheat grains, cereals (Triticum aestivum), neem (Azadirachta indica), ethanol, stearic acid, potassium hydroxide, sodium carbonate, glycerin, water, perfume | Cosmetics/ Cosmeceuticals | N/A | [3,92] |
Commercial hesperidin | N/A | In vivo trials: dermatological assessment, instrumental skin analysis and satisfaction survey | High antioxidant activity; Absorption of UVA, HEV, and IR radiation; Skin barrier functions for protection; Reduction in erythema, skin irritability and visibility of telangiectasia. | Cosmetic product containing hesperidin and SPF 50+ | Cosmetics/ Cosmeceuticals | N/A | [93] |
Hesperidin/ Extract Type | Hesperidin Levels Tested | Testing Model | Main Biological Properties | Formulation | Potential Applications | Molecular Pathways/ Other Relevant Properties | Ref. |
---|---|---|---|---|---|---|---|
Citrus mitis blanco peel water extract | Fraction reach in hesperidin 0.5 mg/mL | In vitro non-cellular assays | Tyrosinase inhibitory activity (IC50 was 3.3 mg/mL). | N/A | Cosmetics/ Cosmeceuticals | N/A | [41] |
Citrus peel extract | 1–50 µg/mL | Melan-a cells | Antioxidant activity DPPH in a dose-dependent manner; Inhibition of tyrosinase activity; Decrease in melanin content in Melan-a in a dose-dependent manner. | N/A | Cosmetics/ Cosmeceuticals | Extract antioxidant activity was greater than vitamin C (control), at the same dosage; Melanogenesis inhibition through suppression of melanosome transport in melanocytes | [45] |
C. unshiu peel-press cakes ethanolic extract | 86 mg/g | B16F10 cells HaCaT cells | No cytotoxic effect on both cell types; Decrease in cellular melanin content and tyrosinase activity in a dose-dependent manner. | N/A | Cosmetics/ Cosmeceuticals | Reduction in α-MSH-stimulated tyrosinase, MTIF protein, TRP-1 and TRP-2 expression in a dose-dependent manner | [66] |
Commercial hesperidin | 0.1–500 μM | B16F10 cells Neonatal Human Melanocytes | No cytotoxic effect up to 40 μM, on both cell types; Reduction in melanin content and tyrosinase activity, in a dose-dependent manner; Radical scavenging activity against DPPH. | N/A | Cosmetics/ Cosmeceuticals | Decrease in tyrosinase, TRP-1 and TRP-2 proteins in a dose-dependent manner; Suppression of melanogenesis through MTIF downregulation and activation of Erk pathways | [81] |
Hesperidin/ Extract Type | Hesperidin Levels Tested | Testing Model | Main Biological Properties | Formulation | Potential Applications | Bioavailability/Molecular Pathways/Other Relevant Properties | Ref. |
---|---|---|---|---|---|---|---|
Commercial hesperidin | 1–10% (w/v) | 3T3 cells Wistar rats S. aureus P. aeruginosa | Hemocompatible; Antimicrobial; Cell proliferation and collagen synthesis increase in a dose-dependent manner; In vivo enhanced performance of would therapy in a dose-dependent manner; Granulation tissue and epidermal proliferation; Wound contraction, epidermal layer formation and remodeling | Alginate/Chitosan/ Hesperidin Hydrogel: 2:1 (v/v) alginate and chitosan solutions (sodium alginate (2% (w/v)) in deionized water; chitosan (2% (w/v)) in 0.5% (v/v) acetic acid) + hesperidin (1 or 10% weight of polymer Alg/Chit) + calcium chloride 50 mM (CaCl2) and 10 μL glutaraldehyde with NaOH 1 M (crosslink). | Skincare Pharmaceutical/ Therapeutic Agent | Neovascularization enhancement in a dose-dependent manner; between 8.9 and 17.2% of hesperidin has been released within the first 3 to 6 h, followed by a sustained release of 77.03 ± 8.71%, over 14 days | [95] |
Commercial hesperidin | 10 mg/mL | Ex vivo goat skin Wistar albino rats | Improvement of therapeutical treatment for anti-inflammatory activity; The gels were close to a neutral pH (6.8), presenting a low risk of skin irritation | Optimal emulsion formulation: 100 mg stearic acid; 50 mg cholesterol, 125 mg soya lecithin; 100 mg hesperidin in 10 mL ethanol. Optimal topical nanoemulgel: Ratio 1:1 of Carbopol to hydroxypropylmethyl cellulose. | Skincare Pharmaceutical/ Therapeutic Agent | Potential as a carrier for topical drug delivery system; the hesperidin release from the optimal emulsion was 98.6% after 6 h; regarding ex vivo permeation studies of hesperidin nanoemulgel, the cumulative drug that permeated through the skin was 98.9% after 4 h | [101] |
Commercial hesperidin | 25–100 µg/mL 1 | Ex vivo rat skin | Hemocompatible; Acceleration of wound closure in a dose-dependent manner; Reduction in inflammation and infection; Improvement of wound contraction, epidermal layer formation, remodeling, and collagen synthesis, in a dose-dependent manner | Hesperidin-loaded PAMAM Dendrimer (Hsp-PAMAM): hesperidin at 2.5, 5, 7.5, or 10% (w/v) was loaded into PAMAM dendrimer. Hsp-PAMAM based hydrogel bandages: sodium alginate; deionized water; chitosan solution and acetic acid. | Skincare Pharmaceutical/ Therapeutic Agent | Safe and compatible for topical delivery; hesperidin shows an outburst pattern in the first 5 h, followed by delayed release, from the bandages; after 24 h, 86.367% of hesperidin was released; rat skin showed a deposition of the drug in the epidermis up to 15–25 µm; the drug was conserved in between the epidermis and dermis, which is ideal for full-thickness wound therapy | [102] |
Commercial hesperidin | 5% (w/v) | Swiss albino mice | Wound-healing acceleration; Enhancement of wound contraction; Induction of cell proliferation | Hydrogel: hesperidin (5 g); deionized water (10 mL) and polyethylene glycol 400 (PEG) (380–420 g/mol). | Skincare Pharmaceutical/ Therapeutic Agent | Increased nitric oxide, glutathione and SOD levels; repression of NF-kB and COX-2 | [103] |
Commercial hesperidin | 0.5% (w/w) | Dermal fibroblasts from donated human skin | Fibroblasts proliferation induction; Migration without terminal differentiation and collagen synthesis; Increased progression of wound confluence and closure | Niacinamide (3.0% w/w), L-carnosine (1.0% w/w), hesperidin (0.5% w/w) and Biofactor HSP® (0.05% w/w). | Skincare Pharmaceutical/ Therapeutic Agent | N/A | [104] |
Commercial hesperidin | 30–120 mM | S. aureus E. coli HUVECs cells Sprague–Dawley rats | Antibacterial; DPPH scavenging activity; No significant cytotoxicity; Cell proliferation and migration activity improvement; Acceleration of wound closure after infection by S. aureus; Re-epithelization enhancement; Stimulation of collagen synthesis and deposition; Stimulation of angiogenesis and hair follicle synthesis | Nanoparticles: silver nitrate (AgNO3) (2 mL, 3.397 mg/mL) and hesperidin solution (10 mL, 17.6 mg/mL). Note: The nanoparticles were Incorporated into a hydrogel. | Skincare Pharmaceutical/ Therapeutic Agent | Activation of basic fibroblast growth factor (bFGF) and Stirt 1 expression; suppression of the expression of pro-inflammatory factors (NF-ƙB, MMP9, TNF-α, and IL-6) | [105] |
Commercial hesperidin | Formulation’s oral intake: 50 mg/kg/day | Sprague–Dawley rats | Necrosis reduction in epidermis and dermis; No congestion or hemorrhage, after 14 days | Oral intake: Bacitracin combined with hesperidin. | Skincare Pharmaceutical/ Therapeutic Agent | Decrease in IL-1 beta and TNF-α levels | [106] |
Commercial hesperidin | 0.5% (w/w) | Sprague–Dawley rats | Reduction in wound surface area; Increased wound contraction; Potentiation of wound epithelization by the 28th day; Promotion of cellular infiltration and proliferation | Scaffold: collagen in 0.05-M acetic acid (0.6% (w/w)), chondroitin-6-sulfate (in 0.05-macetic acid). Scaffolds in cosmeceutical formulation: niacinamide (3.0% w/w), L-carnosine (1.0% w/w), hesperidin (0.5% w/w) and Biofactor HSP®(0.05% w/w). Scaffolds crosslinking: 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide and N-hydroxysuccinimide (EDAC/NHS) and 0.5% glutaraldehyde (GA). | Skincare Pharmaceutical/ Therapeutic Agent | N/A | [107] |
Commercial hesperidin | Oral intake: 25–100 mg/kg/day | Sprague–Dawley rats | Wound half-closure time improvement in a dose-dependent manner; Oxido-nitrosative stress reduction; Hydroxyproline levels (collagen synthesis marker) increase; Angiogenesis and re-epithelization induction | N/A | Skincare Pharmaceutical/ Therapeutic Agent | VEGF-c, Ang-1, Tie-2, TGF-β and Smad 2/3 mRNA expression upregulation | [108,109] |
Commercial hesperidin | Oral intake: 10–80 mg/kg/day | Rats | Wound healing promoted in Diabetes-induced animals; Wound half-closure time improvement | N/A | Skincare Pharmaceutical/ Therapeutic Agent | Reduction in MDA, MPO, TNF-α, and IL-6 levels in a dose-dependent manner; stimulation of VEGF, GSH, HDP, and SOD expression in a dose-dependent manner | [110] |
Commercial hesperidin | 5–10% (w/w) | Swiss albino mice | Epithelization time reduction; Enhancement of wound contraction; Wound-healing activity improved in a dose-dependent manner in the S.aureus infected wound model (antibacterial activity) | Ointments containing: 5% (w/w) or 10% (w/w) hesperidin. | Skincare Pharmaceutical/ Therapeutic Agent | N/A | [111] |
Commercial hesperidin | 50–250 µg/mL 2 | In vitro non-cellular assays | Strong DPPH scavenging activity | Nanoparticles optimal formulation: hesperidin (15 mg); chitosan (20 mg); soya lecithin (10 mg) and surfactant (1 mL) | Skincare Pharmaceutical/ Therapeutic Agent | In vitro, hesperidin presents an outburst pattern in the first 4 h followed by delayed release from nanoparticles; the optimal formulation was stable, safe to use and could improve the topical bioavailability of hesperidin due to its nano-size with a larger surface area; the formulation is a suitable hesperidin delivery agent, leading to improved wound healing | [112] |
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Rodrigues, C.V.; Pintado, M. Hesperidin from Orange Peel as a Promising Skincare Bioactive: An Overview. Int. J. Mol. Sci. 2024, 25, 1890. https://doi.org/10.3390/ijms25031890
Rodrigues CV, Pintado M. Hesperidin from Orange Peel as a Promising Skincare Bioactive: An Overview. International Journal of Molecular Sciences. 2024; 25(3):1890. https://doi.org/10.3390/ijms25031890
Chicago/Turabian StyleRodrigues, Cristina V., and Manuela Pintado. 2024. "Hesperidin from Orange Peel as a Promising Skincare Bioactive: An Overview" International Journal of Molecular Sciences 25, no. 3: 1890. https://doi.org/10.3390/ijms25031890
APA StyleRodrigues, C. V., & Pintado, M. (2024). Hesperidin from Orange Peel as a Promising Skincare Bioactive: An Overview. International Journal of Molecular Sciences, 25(3), 1890. https://doi.org/10.3390/ijms25031890