**1. Introduction**

Cardiovascular disease (CVD) represents a major cause of death in Europe, North America, and in some parts of Asia [1–4]. According to the World Health Organization 2016 records, CVD accounted for 31% of the total global mortality [5]. This knowledge has empowered today's consumers to be selective at identifying foods that have both adequate essential nutrient contents to meet daily requirements while also providing distinct health benefits attributed to plant-based bioactives that can protect against CVD. Examples of bioactive food constituents that lower serum cholesterol are plant sterols [6–8] and, also, pigmented anthocyanins that display antioxidant and anti-inflammatory properties [9–12], the combination of which could have a greater role in protecting against CVD. Hypercholesterolemia, along with a disturbed antioxidant status and onset of inflammation, are major underlying causes of CVD.

Phytosterols are natural ingredients present in vegetable oils and, also, can be recovered from wood sources. Phytosterol intake from a traditional Western diet depends on personal habits and geographical location [13]. A typical Western diet contains about 300 mg/day of phytosterols [13–15]. Plant sterols and stanols are structurally similar to cholesterol (Figure 1) [16] and are effective at lowering the plasma total and low-density lipoprotein cholesterol [7,17,18].

**Figure 1.** Chemical structures of (**a**) cholesterol, (**b**) campesterol, (**c**) β-sitosterol, and (**d**) β-sitostanol.

Black rice, on the other hand, is an excellent source of anthocyanidins, in addition to dietary fiber, flavonoids, and other polyphenols. Rice oil contains nonatherogenic fatty acids [19,20] and is also a good source of plant sterols, such as oryzanol. These bioactive components are unsaponifiable, nonglyceride components [20], which contribute to cholesterol-lowering effects reported in many animal and human studies [19–24]. The pigment from black rice contains two major anthocyanins—namely, cyanidin-3-*O*-glucoside and peonidin-3-*O*-glucoside—the former being predominant [10,23,25] (Figure 2).

**Figure 2.** Structures of cyanidin-3-*O*-glucoside (**a**) and peonidin-3-*O*-glucoside (**b**).

Anthocyanins are naturally occurring phenolic compounds that provide color and bioactive properties, such as antioxidants [10] and lowering of serum cholesterol and triacyglycerides in rats, when fed to rats on a daily basis [26].

There are no studies that have examined the effects of consuming a combination of these bioactive agents to mitigate the changes of known CVD risk factors induced by feeding on an atherogenic diet. The objective of the present study was to demonstrate a potential interaction or added effect of combining a standardized cyanidin-3-*O*-glucoside black rice fraction (BRF) and a known wood sterol (WS) mixture to protect against elevated serum lipids and, moreover, target tissue cholesterol deposition in rats fed an atherogenic diet.
