| In vivo: |
| Photochem Photobiol Sci. 2016 Apr;15(4):554-63. | | Topical formulation containing hesperidin methyl chalcone inhibits skin oxidative stress and inflammation induced by ultraviolet B irradiation.[Pubmed: 27021784] | Skin exposure to ultraviolet B (UVB) irradiation has increased significantly in recent years due to ozone depletion, and it represents the main cause of many skin diseases. Hesperidin methylchalcone (HMC) is a compound used to treat vascular diseases that has demonstrated anti-inflammatory activities in pre-clinical studies.
METHODS AND RESULTS:
Herein, we tested the antioxidant activity of HMC in cell free systems and the in vivo effects of a stable topical formulation containing HMC in a mouse model of skin oxidative stress and inflammation induced by UVB irradiation. HMC presented ferric reducing power, neutralized 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and hydroxyl free radicals, and inhibited lipid peroxidation. In hairless mice, a topical formulation containing HMC inhibited UVB irradiation-induced skin edema, depletion of antioxidant capacity (ferric and ABTS reducing abilities and catalase activity), lipid peroxidation, superoxide anion production and mRNA expression of gp91phox (nicotinamide adenine dinucleotide phosphate [NADPH] oxidase 2 sub-unity). In addition, HMC inhibited UVB irradiation-induced depletion of reduced glutathione levels by maintaining glutathione peroxidase-1 and glutathione reductase mRNA expression, prevented down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression and increased heme oxygenase-1 mRNA expression. Finally, we demonstrated that topical application of the formulation containing HMC inhibited cytokine (TNF-α, IL-1β, IL-6, and IL-10) production induced by UVB irradiation.
CONCLUSIONS:
Therefore, this topical formulation containing HMC is a promising new therapeutic approach to protecting the skin from the deleterious effects of UVB irradiation. | | Chem Biol Interact. 2015 Feb 25;228:88-99. | | Protective effects of the flavonoid hesperidin methyl chalcone in inflammation and pain in mice: role of TRPV1, oxidative stress, cytokines and NF-κB.[Pubmed: 25617481 ] | Cytokines and reactive oxygen species are inflammatory mediators that lead to increased sensitivity to painful stimuli, and their inhibition represents a therapeutic approach in controlling acute and chronic pain. The water-soluble flavonone hesperidin methylchalcone (HMC) is used in the treatment of venous diseases, but its bioactivity as anti-inflammatory and analgesic is poorly understood. The present study evaluated the protective effects of HMC in widely used mouse models of acute and prolonged inflammation and pain.
METHODS AND RESULTS:
Male Swiss mice were treated with HMC (3-100 or 30 mg/kg, intraperitoneally) or vehicle (saline) 1h before inflammatory stimuli. In overt pain-like behavior tests, HMC inhibited acetic acid- and phenyl-p-benzoquinone-induced writhing, and capsaicin-, Complete Freund's Adjuvant (CFA)- and formalin-induced paw flinching and licking. HMC also inhibited carrageenan-, capsaicin- and CFA-induced mechanical and thermal hyperalgesia. Mechanistically, HMC inhibited carrageenan-induced cytokine (TNF-α, IL-1β, IL-6, and IL-10) production, oxidative stress and NF-κB activation. Furthermore, HMC did not cause gastric or hepatic injury in a 7 days treatment protocol.
CONCLUSIONS:
Thus, this is the first report that HMC reduces inflammation and inflammatory pain by targeting TRPV1 (transient receptor potential vanilloid type 1) receptor activity, oxidative stress, cytokine production, and NF-κB activity, which suggests its potential applicability in inflammatory diseases. | | J Cardiovasc Pharmacol. 1993 Aug;22(2):225-30. | | Inhibitory effect of the Ruscus extract and of the flavonoid hesperidine methylchalcone on increased microvascular permeability induced by various agents in the hamster cheek pouch.[Pubmed: 7692162] | The Ruscus extract and the flavonoid Hesperidin methylchalcone
(HMC) are used in treatment of venous insufficiency. In the present study, we used the hamster cheek pouch preparation and investigated the effects of these substances on increased microvascular permeability induced by bradykinin, histamine, and leukotriene B4 (LTB4) applied topically.
METHODS AND RESULTS:
Experiments were performed on male hamsters; 30 min after completion of the cheek pouch preparation, fluorescein-labeled dextran [molecular weight (mol wt) 150,000] was given intravenously (i.v.). Bradykinin, histamine, and LTB4 increased the number of fluorescent vascular leakage sites from postcapillary venules, evidence for an increase in macromolecular permeability, which was quantified in ultraviolet (UV)-light microscope as the number of leaky sites in the prepared area. Ruscus extract and HMC, given i.v., significantly inhibited the macromolecular permeability-increasing effect of bradykinin, LTB4, and histamine. Ruscus extract, applied topically, dose dependently inhibited the macromolecular permeability-increasing effect of histamine.
CONCLUSIONS:
Our results show that Ruscus extract and HMC have a protective effect against leakage of FITC-dextran in the cheek pouch after administration of various permeability-increasing substances, which further supports data previously reported on patients with venous insufficiency. |
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