Advances in Biosynthesis, Pharmacology, and Pharmacokinetics of Pinocembrin, a Promising Natural Small-Molecule Drug

Abstract

Pinocembrin is one of the most abundant flavonoids in propolis, and it may also be widely found in a variety of plants. In addition to natural extraction, pinocembrin can be obtained by biosynthesis. Biosynthesis efficiency can be improved by a metabolic engineering strategy and a two-phase pH fermentation strategy. Pinocembrin poses an interest for its remarkable pharmacological activities, such as neuroprotection, anti-oxidation, and anti-inflammation. Studies have shown that pinocembrin works excellently in treating ischemic stroke. Pinocembrin can reduce nerve damage in the ischemic area and reduce mitochondrial dysfunction and the degree of oxidative stress. Given its significant efficacy in cerebral ischemia, pinocembrin has been approved by China Food and Drug Administration (CFDA) as a new treatment drug for ischemic stroke and is currently in progress in phase II clinical trials. Research has shown that pinocembrin can be absorbed rapidly in the body and easily cross the blood–brain barrier. In addition, the absorption/elimination process of pinocembrin occurs rapidly and shows no serious accumulation in the body. Pinocembrin has also been found to play a role in Parkinson’s disease, Alzheimer’s disease, and specific solid tumors, but its mechanisms of action require in-depth studies. In this review, we summarized the latest 10 years of studies on the biosynthesis, pharmacological activities, and pharmacokinetics of pinocembrin, focusing on its effects on certain diseases, aiming to explore its targets, explaining possible mechanisms of action, and finding potential therapeutic applications.

Apitherapy for Age-Related Skeletal Muscle Dysfunction (Sarcopenia): A Review on the Effects of Royal Jelly, Propolis, and Bee Pollen

“…Existing knowledge denotes no adverse effects from their consumption either in rodents or in humans [ 39 , 66 ]. The safety of pinocembrin, a flavonoid available in propolis and an approved drug in China, is documented since its elimination from the body is rapid [ 91 ]. The safety profile of bee pollen (both crude and processed) has been empirically tested.…”

Apitherapy for Parkinson’s Disease: A Focus on the Effects of Propolis and Royal Jelly

“…All these substances are flavonoids that exist in multiple plants, and they possess strong free radical scavenging potential, on top of many other biological activities, e.g., immunomodulatory, anti-inflammatory, antiviral, and ant-neoplastic [ 42 – 45 ]. PB easily crosses the bloodbrain barrier and produces neuroprotective, antioxidant, and anti-inflammatory activities, which allowed its approval by China Food and Drug Administration as a treatment for ischemic stroke [ 46 ].…”

“…Because of its rich chemical composition, propolis has a wide range of several other therapeutic activities: antibacterial, antiviral, antifungal, anti-inflammatory, and anticarcinogenic anticholesterol properties [ 29 , 36 , 38 , 41 , 47 , 48 ]. Accordingly, propolis and its components have been used to promote wound healing and to treat several diseased conditions such as pulp problems, oral candidiasis, genital herpes, and ischemic stroke, to name a few [ 38 , 39 , 46 , 48 ].…”

Growing Importance of Natural Products Research

“…Studied were also the effect of enzymolysis on the performance of soy protein-based adhesive [8] and the study of new octadecanoid enantiomers from the whole plants of Plantago depressa [9]. Connected studies that combined the biological properties of another type of secondary metabolite described the biosynthesis of fluorescent β subunits of C-phycocyanin from Spirulina subsalsa in Escherichia coli, and their antioxidant properties [10] and presented the synthesis of the sex pheromone of the tea tussock moth based on a resource chemistry strategy [11].Review articles described well the synthesis and anticancer activity of CDDO and CDDO-Me, two derivatives of natural triterpenoids [12], the advances in biosynthesis, pharmacology, and pharmacokinetics of pinocembrin, a promising natural small-molecule drug [13], as well as recent advances in the discovery and biosynthetic study of eukaryotic RiPP natural products [14]. Another review article addressed the issue of whether polyphenols could help in the control of rheumatoid arthritis [15].Summing up, the current development in the chemistry of natural products proved to be so exciting that now Molecules itself organized recently several special issues oriented to this unfinished…”

“…Review articles described well the synthesis and anticancer activity of CDDO and CDDO-Me, two derivatives of natural triterpenoids [12], the advances in biosynthesis, pharmacology, and pharmacokinetics of pinocembrin, a promising natural small-molecule drug [13], as well as recent advances in the discovery and biosynthetic study of eukaryotic RiPP natural products [14]. Another review article addressed the issue of whether polyphenols could help in the control of rheumatoid arthritis [15].…”