Therapeutic effects of hidrosmin on chronic venous insufficiency of the lower limbs

Domínguez, Carlos; Brautigam, I; González, Eva Gallego; González, Julia; Nazco, J; Valiente, Román; Boada, J

doi:10.1185/03007999209111529

Cited by 18 publications

(4 citation statements)

References 6 publications

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“…Flavonoid compounds seem to be a promising alternative to treat chronic DM complications due to their outstanding pharmacological effects including anti-inflammatory, antioxidant, antidiabetic, and antihypertensive, as evinced in experimental models and clinical studies [ 20 , 33 , 34 ]. The synthetic flavonoid hidrosmin, a diosmin-derived flavone with vasoprotective effects [ 35 ], is a venotonic agent used for many years in patients suffering from chronic venous insufficiency mainly due to its antiedematous properties and other beneficial effects (i.e., in swelling and leg cramps), more effective in some cases than diosmin [ 21 , 36 ]; however, the therapeutic effects of hidrosmin in other chronic diseases remains to be explored. This study is the first preclinical evaluation of the effects and underlying mechanisms of hidrosmin therapy in diabetic-induced kidney disease.…”

Section: Discussionmentioning

confidence: 99%

“…Hidrosmin is a synthetic flavonoid developed for the treatment of venous insufficiency [ 21 , 22 ] ( Supplementary Figure S1 ). Hidrosmin is derived from diosmin, a hesperidin-derivative bioflavonoid whose antioxidant, anti-inflammatory, antihypertensive, and anti-ischemic properties have been studied in several experimental models [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

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Nephroprotective Effects of Synthetic Flavonoid Hidrosmin in Experimental Diabetic Nephropathy

et al. 2021

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Diabetes mellitus (DM) is a high-impact disease commonly characterized by hyperglycemia, inflammation, and oxidative stress. Diabetic nephropathy (DN) is a common diabetic microvascular complication and the leading cause of chronic kidney disease worldwide. This study investigates the protective effects of the synthetic flavonoid hidrosmin (5-O-(beta-hydroxyethyl) diosmin) in experimental DN induced by streptozotocin injection in apolipoprotein E deficient mice. Oral administration of hidrosmin (300 mg/kg/day, n = 11) to diabetic mice for 7 weeks markedly reduced albuminuria (albumin-to-creatinine ratio: 47 ± 11% vs. control) and ameliorated renal pathological damage and expression of kidney injury markers. Kidneys of hidrosmin-treated mice exhibited lower content of macrophages and T cells, reduced expression of cytokines and chemokines, and attenuated inflammatory signaling pathways. Hidrosmin treatment improved the redox balance by reducing prooxidant enzymes and enhancing antioxidant genes, and also decreased senescence markers in diabetic kidneys. In vitro, hidrosmin dose-dependently reduced the expression of inflammatory and oxidative genes in tubuloepithelial cells exposed to either high-glucose or cytokines, with no evidence of cytotoxicity at effective concentrations. In conclusion, the synthetic flavonoid hidrosmin exerts a beneficial effect against DN by reducing inflammation, oxidative stress, and senescence pathways. Hidrosmin could have a potential role as a coadjutant therapy for the chronic complications of DM.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nephroprotective Effects of Synthetic Flavonoid Hidrosmin in Experimental Diabetic Nephropathy

et al. 2021

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“…Diosmin and hidrosmin are generally very well tolerated. The Cochrane analysis pooled eight randomized placebo controlled studies 34,[38][39][40]42,46,47,48 reporting adverse effects with equal frequency in both the treatment (50/424, 11.8%) and placebo arms (49/413, 11.9%); risk ratio 1.01, 95% CI 0.70-1.44). 31 In these eight studies, 12 patients withdrew from treatment in the treatment arms and 11 in the placebo.…”

Section: Adverse Effectsmentioning

confidence: 99%

Recommendations for the medical management of chronic venous disease: The role of Micronized Purified Flavanoid Fraction (MPFF)

Bush¹,

Comerota²,

Meissner

et al. 2017

Phlebology

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Scope A systematic review of the clinical literature concerning medical management of chronic venous disease with the venoactive therapy Micronized Purified Flavonoid Fraction was conducted in addition to an investigation of the hemodynamics and mechanism of chronic venous disease. Methods The systematic review of the literature focused on the use of Micronized Purified Flavonoid Fraction (diosmin) which has recently become available in the US, in the management of chronic venous disease. The primary goal was to assess the level of evidence of the role of Micronized Purified Flavonoid Fraction in the healing of ulcers, and secondarily on the improvement of the symptoms of chronic venous disease such as edema. An initial search of Medline, Cochrane Database for Systematic Reviews and Google Scholar databases was conducted. The references of articles obtained in the primary search, including a Cochrane review of phlebotonics for venous insufficiency, were reviewed for additional studies. Studies were included if patients had a diagnosis of chronic venous disease documented with Doppler and Impedance Plethysmography. Studies excluded were those that had patients with arterial insufficiency (Ankle Brachial Index < .6), comorbidity of diabetes, obesity, rheumatological diseases, or if other causes of edema were present (congestive heart failure, renal, hepatic or lymphatic cause), or if the patient population had recent surgery or deep vein thrombosis, or had been using diuretics (in studies of edema). Other elements of the study design were to note specifically the type of compression therapy used in conjunction with Micronized Purified Flavonoid Fraction. Results The literature review yielded 250 abstracts, 65 of which met criteria for further review and 10 papers were selected for consideration in the systematic review. Conclusion In summary, the general level of evidence supports the recommendation that the use of medical therapy with Micronized Purified Flavonoid Fraction has beneficial outcomes without serious adverse events. In the United States, diosmiplex is the only available prescription formulation of Micronized Purified Flavonoid Fraction. It is derived from the rinds of oranges and is categorized as a medical food and not as a drug; and may be a particularly attractive therapy for many chronic venous disease patients because of its favorable safety profile. The Working Group for chronic venous disease concurs with previous guidance by the International European Society for Vascular Surgery in 2015 which recommended the use of Micronized Purified Flavonoid Fraction for the healing of venous ulcers, alone and adjunctive to compression therapy, and for the reduction in symptoms of chronic venous disease such as edema.

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“…Epigallocatechin gallate (EGCG) has been investigated for Parkinson's disease (Zhou et al, 2018), fatty liver disease (Chen et al, 2018), diabetes (Feng et al, 2018), cardiovascular and metabolic disorders (Eng et al, 2018), and various cancers (Enkhbat et al, 2018;Negri et al, 2018;Zhu etal., 2019). Hidrosmin has also been investigated for chronic venous insufficiency (Honorato and Arcas, 1990;Dominguez et al, 1992), and chronic lymphedema (Jimenez , 1991). Catechin gallate, another green tea flavonoid, has similar properties of EGCG in terms of cholesterol reduction (Ikeda etal., 2003).…”

Section: Findings From This Studymentioning

confidence: 99%

Covid-19 and Flavonoids: In silico Molecular Dynamics Docking to the Active Catalytic Site of SARS-CoV and SARS-CoV-2 Main Protease

Peterson¹

2022

AFJPS

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Inhibition of the main protease 3CLpro of SARS-CoV and SARS-CoV-2 is being targeted in the search for antivirals to shorten patient recovery times from Covid-19 disease. We investigated 72 flavonoids for their potential to bind with the active catalytic site of 3CLpro for SARS-CoV and SARS-CoV-2. In silico molecular dynamics docking was performed using energy-minimized states of the flavonoids. Three variants of the active catalytic site of the protease 3CLpro were used: one based on x-ray crystallography for SARS-CoV, the second based on x-ray crystallography for SARS-CoV-2, and the third based on a 3D-modeled form of an amino acid sequence alignment of SARS-CoV-2 3CLpro from 8 humans. Docking involved characterization of the best putative pose in the "pocket" of the active site based on altering rotatable bonds in each molecule. The binding energy (kcal/mol) and number of hydrogen bonds were assessed during each pose. Mean binding energy across the 3 variants of 3CLpro was sorted in ascending order to rank each flavonoid, since more negative values indicate stronger binding. The top 10 flavonoids identified were amentoflavone, gallocatechin gallate, diosmin, epigallocatechin gallate, hidrosmin, catechin gallate, elsamitrucin, pectolinaren, quercetin, and isoquercetin. Other flavonoids investigated with significant binding energies were hesperidin, rutin, rhoifolin, and peurarin. In vivo animal research is now needed for evaluating whether these flavonoids can minimize early infection and alleviate symptoms and shorten recovery times for late-stage Covid-19 disease. Human prevention trials for minimizing early infection and combination therapy trials with antivirals for shortening recovery times in late-stage Covid-19 disease could also be pursued.

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Therapeutic effects of hidrosmin on chronic venous insufficiency of the lower limbs

Cited by 18 publications

References 6 publications

Nephroprotective Effects of Synthetic Flavonoid Hidrosmin in Experimental Diabetic Nephropathy

Nephroprotective Effects of Synthetic Flavonoid Hidrosmin in Experimental Diabetic Nephropathy

Recommendations for the medical management of chronic venous disease: The role of Micronized Purified Flavanoid Fraction (MPFF)

Covid-19 and Flavonoids: In silico Molecular Dynamics Docking to the Active Catalytic Site of SARS-CoV and SARS-CoV-2 Main Protease

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