Table 5.
Biological activities of commercial and orange peel’s hesperidin related to skin cancer and other skin 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] |
HCT-116—colorectal adenocarcinoma cell line. MCF-7—mammary adenocarcinoma cell line. HepG2—hepatocellular carcinoma cell line. A431—epidermoid carcinoma cell line. A375/CHL01/SKMEL147—human melanoma cell lines; N/A—non-added.