Dihydromyricetin: A review on identification and quantification methods, biological activities, chemical stability, metabolism and approaches to enhance its bioavailability

Abstract

Background: Dihydromyricetin (DMY) is an important plant flavonoid, which has received great attention due to its health-benefiting activities, including antioxidant, antimicrobial, anti-inflammatory, anticancer, antidiabetic and neuroprotective activities. DMY capsules have been sold in US as a nutraceutical supplement to prevent alcoholic hangovers. The major disadvantage associated with DMY is its chemical instability and poor bioavailability caused by the combined effects of its low solubility and poor membrane permeability. This limits its practical use in the food and pharmaceutical fields. Scope and approach: The present paper gives an overview of the current methods for the identification and quantification of DMY. Furthermore, recent findings regarding the main biological properties and chemical stability of DMY, the metabolism of DMY as well as different approaches to increase DMY bioavailability in both aqueous and lipid phases are discussed. Key findings and conclusions: Current trends on identification and quantification of DMY have been focused on spectral and chromatographic techniques. Many factors such as heat, pH, metal ions, could affect the chemical stability of DMY. Despite the diverse biological effects of DMY, DMY faces with the problem of poor bioavailability. Utilization of different delivery systems including solid dispersion, nanocapsule, microemuslion, cyclodextrin inclusion complexes, co-crystallization, phospholipid complexes, and chemical or enzymatic acylation has the potential to improve both the solubility and bioavailability. DMY digested in laboratory animals undergoes reduction, dehydroxylation, methylation, glucuronidation, and sulfation. Novel DMY delivery systems and basic pharmacokinetic studies of encapsulated DMY on higher animals and humans might be required in the future.

Dihydromyricetin Acts as a Potential Redox Balance Mediator in Cancer Chemoprevention

“…At a concentration of 20 μg/mL, DHM was stable at room temperature after 12 h and at -20°C for 10 d, but only 45.42% was retained after 3 h in simulated intestinal fluid at 37°C [21]. The plasma DHM concentration reached maximum (159 μg/L) at 1.5 h postadministration when DHM powder was given at a dosage of 115 mg/kg body weight in rabbits, indicating a low bioavailability of DHM [18]. Efflux transporters, multidrug resistance protein 2, and breast cancer resistance protein also played an important role in DHM uptake and transport processes [22].…”

“…The biological properties and the underlying mechanisms of DHM were investigated mostly by in vitro cell cultures and in vivo animal models. In addition, DHM was reported as toxicologically safe and could effectively reverse multidrug resistance [15][16][17][18][19]. Hence, DHM is a promising bioactive compound for developing healthy/functional foods.…”

Hovenia dulcis Thumberg: Phytochemistry, Pharmacology, Toxicology and Regulatory Framework for Its Use in the European Union

“…In 2018, Dong et al proposed a mechanism of action concerning the hepatoprotective activity of H. dulcis fruit extract, and a further study of the same authors elucidated the direct involvement of DHM in the metabolism of acetaminophen endowing the use of fruits as an herbal remedy for preventing acetaminophen-induced liver injury [ 22 , 23 ]. The potential application of DHM as a drug or active component in food supplements is limited by its poor chemical stability and poor bioavailability [ 24 ]; however, in the last decade, new drug delivery systems have been proposed to overcome these disadvantages [ 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. DHM is responsible for other pharmacological activities not related to H. dulcis , and thus that are not discussed in this paper [ 32 ].…”

Molecular Level Insight Into the Benefit of Myricetin and Dihydromyricetin Uptake in Patients With Alzheimer’s Diseases

“…For instance, MYR, has been reported to be abundant in strawberries, apples, spinach, aloe vera, carrots (Zhang et al, 2015), mulberries (Mahmood et al, 2012), etc., and the content of MYR in red wine can reach twice that of resveratrol (Lee et al, 2007;Rodrigo et al, 2011). Dihydromyricetin is widely found in grapes, bayberry, ampelopsis (Clementi et al, 2015), ginkgo and other plants, with the content of DMY in rattan tea particularly is high, often reaching 30-40% (Liu et al, 2019). Moreover, MYR is listed as a health product in Europe, and has been approved by the FDA for pharmaceuticals, foods, and health products in the United States with FYI, a health product containing myricetin being successfully launched (Whitehouse, 2002).…”