**1. Introduction**

Pterostilbene (PTS) (trans-3,5-dimethoxy-4 -hydroxystilbene) is a natural polyphenol and a dimethyl ether analog of resveratrol [1]. PTS is produced by plants as a secondary metabolite that serves to respond to environmental challenges, including UV radiation, drought, fluctuating temperature extremes, grazing pressures, and fungal infections, and PTS serves as an important mediator of disease resistance [2,3]. Similar to resveratrol, PTS also behaves as a phytoalexin, conferring crucial anti-pathogenic defense to plants [4,5]. The daily consumption of PTS is determined by its dietary intake. Based on the type of blueberry ingested, the content of PTS is estimated to range from 99 ng to 520 ng/gram of fruit [6]. Though berries are the most evident source of PTS, it has been reported to be present in various other food sources, including peanuts.

As a natural dietary component, PTS has been documented to exhibit an increased bioavailability compared to other stilbene compounds, which further highlights the need to study the clinical potential of this compound in medical conditions [7,8]. Various evidence has demonstrated the effect of PTS in countering oxidative damage and inflammation, imparting preventive and therapeutic benefits in experimental disease models [4,7,9].

**Citation:** Nagarajan, S.; Mohandas, S.; Ganesan, K.; Xu, B.; Ramkumar, K.M. New Insights into Dietary Pterostilbene: Sources, Metabolism, and Health Promotion Effects. *Molecules* **2022**, *27*, 6316. https:// doi.org/10.3390/molecules27196316

Academic Editor: Nour Eddine Es-Safi

Received: 6 September 2022 Accepted: 21 September 2022 Published: 25 September 2022

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Indeed, through its antioxidant and anti-inflammatory activity, PTS has been reported to regulate pathogenic pathways associated with carcinogenesis, hematologic diseases, neurological disorders, vascular dysfunction, aging disorders, and diabetes [7].

Among the identified polyphenols, resveratrol has been determined to exhibit relatively poor oral bioavailability and undergoes rapid first-pass metabolism. On the contrary, methylated polyphenols such as PTS have been documented to possess better intestinal absorption and elevated hepatic stability. Considering the potential drawbacks that are exhibited due to the unfavorable pharmacodynamics of resveratrol, much focus has shifted towards understanding and characterizing the pharmacokinetics and therapeutic potential of PTS. Overall, this review provides evidence that PTS is a promising, novel, potent, and safe drug candidate for treating various diseases and disorders.

### **2. Potential Dietary Sources of PTS**

Various human diet crops have been documented to produce PTS at varying levels (Table 1). Red sandalwood, also referred to as Heartwood (*Pterocarpus santalinus*), was the first identified source of PTS [3]. Of note, contrary to flavonoids, which are produced by many plants, stilbenes are synthesized by only a few plant species (Table 1). PTS has been reported to be abundantly found in Indian Kino (*Pterocarpus marsupium*), *Guibourtia tessmannii*, and *Vaccinium* spp. berries and at relatively lower levels in the leaves of grape (*Vitis vinifera*) and blueberry fruits [9,10]. The concentration ranges from 9.9 to 15.1 mg/kg of blueberries, 0.2 to 4.7 mg/g of the weight of the skin of fungus-infected grapes, 99 to 151 ng/g dried sample of rabbit-eye blueberry (*Vaccinium ashei*), and 520 ng/g dried sample of deerberries (*Vaccinium stamineum*) [11]. Additionally, peanut (*Arachis hypogaea*) has also been identified as a source of PTS [12] (Table 1). However, it should be noted that the amount of PTS in many of these food sources may be insufficient to provide documented health benefits. Dietary supplements of the formulated pure compound offer a solution to provide sufficient nutritional levels. Moreover, considering the growing interest in PTS as a promising nutraceutical compound, further research that aims to identify the compound in fresh and processed food products by employing standardized extraction and analytical methods is warranted.


**Table 1.** Potential Sources of Pterostilbene.
