**1. Introduction**

The plant kingdom continues to hold considerable importance in our daily life. In addition to supplying humanity with food, it is considered as a potential source of thousands of novel materials such as fragrances, flavoring agents, dyes, fibers, beverages, building materials, heavy metal chelators, and many useful compounds of great therapeutic value.

Early studies of plants helped humankind make use of local flora for healing ailments. These studies have continued until now to seek out new agents for the treatment of various diseases. Recent investigations regarding plants with centuries of use in folk medicine have generated a great deal of information about the biologically active chemical components responsible for many claimed medicinal effects. As a result of thorough research involving the isolation and structure characterization techniques, many lead compounds, and prototypes from natural products have assumed reputable roles in medicine. Despite

**Citation:** Gad, H.A.; Roberts, A.; Hamzi, S.H.; Gad, H.A.; Touiss, I.; Altyar, A.E.; Kensara, O.A.; Ashour, M.L. Jojoba Oil: An Updated Comprehensive Review on Chemistry, Pharmaceutical Uses, and Toxicity. *Polymers* **2021**, *13*, 1711. https://doi.org/10.3390/polym 13111711

Academic Editor: Bramasta Nugraha

Received: 28 April 2021 Accepted: 21 May 2021 Published: 24 May 2021

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the huge number of synthetic and semisynthetic drugs, the most valuable medicinal agents still in use are obtained from medicinal plants.

There is high consumption of natural resources due to the increasing population. The resultant demand for green energy amidst fossil fuel shortages has rekindled interest in Jojoba oil (*Simmondsia chinensis* (Link) Schneider). Jojoba oil is the only unsaturated liquid wax readily extractable in large quantities from plant sources (≈52% of the total seed weight), which shows a high structure similarity with the sperm whale oil. This similarity has increased the interest in Jojoba oil as a replacement for sperm whale oil (spermaceti wax) since the 1970s [1].

*Simmondsia chinensis* (Link) Schneider is native to North and Central American deserts but cultivated worldwide in Chile, Egypt, and Argentina [2]. Jojoba was widely used by Native Americans in the Sonora desert (California) as a foodstuff in the form of cooked fruits and in oil form as a therapeutic for multiple ailments: cancer therapy, liver and kidney disorders, obesity, parturition, sore throat, superficial wound healing, warts, psoriasis, acne, sunburn, and treatment of poison ivy exposure [3–6]. Jojoba oil is widely used in the pharmaceutical industry, especially in cosmetics, to restore the ordinary health of hair and skin. The leaf extract, combined with extracts from other plants, also acts as antiinflammatory agents to treat sensitive skin stress [7]. Jojoba cosmetic products currently on the market include the following: bath oil, body oil, cleansing creams, cleansing pads, cleansing scrubs, nourishing facial cream, facial oil, hair conditioner, hair oil, makeup remover, and shaving cream [8–11].

In addition, the oil has many industrial applications that include an extreme temperature/extreme pressure lubricant in the form of sulfurized oil, which can bear high temperature and pressure without changing its viscosity [6,12]. Other industrial uses include the extraction and separation of isotopes such as Uranium (VI), Thorium (IV), and Plutonium (IV); in the leather industry as a fat liquor with good tanning properties [5]; as a surfactant, fire retardant, lamp oil, candle wax, polishes [13], and antifoaming agents in isolation of penicillin and tetracycline [9].

An updated and in-depth review about jojoba oil chemistry, its pharmaceutical and industrial uses, and toxicity was conducted and is presented in this work to supplement the lack of comprehensive reviews covering the plant since the 1990s. The keywords jojoba, *Simmondsia*, chemistry, pharmaceutical preparations, emulgels, nanoparticles, toxicity, and biological activity were used in many combinations to search Scifinder®, PubMed®, Web of Science ® starting 1990 until 2021. English language was used as the only filter.

#### **2. Common Names and Botanical Characteristics**

The word jojoba, pronounced "ho-ho-ba", is a distortion of the native Papago Indian word "howhowi". Jojoba is known by many other names such as bucknut, coffee nut, goatnut, pignut, nutpush, goatberry, sheepnut, and lemon leaf [14]. The seeds of the jojoba plant are dark brown, akin to large coffee beans.

Plants of the order Euphorbiales are usually herbs, shrubs, or sometimes trees [15]. They are widely distributed globally, especially in temperate, subtropical, and tropical regions [16]. They have frequently unisexual (rarely bisexual) hypogynous flowers, which are generally regular with a single whorl of a green perianth. The stamens are equal in number to perianth leaves or numerous. The pistil is composed of three carpels forming a trilocular ovary, with each chamber containing one or two anatropous, pendulous ovules in the inner angle with ventral or dorsal raphe [17]. Simmondsiaceae is a small family of one genus, *Simmondsia*, which is abundant in Southern Arizona, Sonora, and Baja California. Plants that belong to "Simmondsiaceae" are mostly woody branched shrubs that reach 2–4 m in height [4–6]. A photograph of male and female trees, flowers, and seeds of *Simmondsia chinensis* are displayed in Figure 1.

reach 2–4 m in height [4–6]. A photograph of male and female trees, flowers, and seeds of

*Simmondsia chinensis* are displayed in Figure 1.

**Figure 1.** A photograph showing different organs of *Simmondsia chinensis*, (**A**) Branch of the plant (X 0.8), (**B**) Male flowers (X 1.0), (**C**) Old male and female trees (X 0.02), (**D**) Female flower (X 0.5), (**E**) Ripe fruit (X 0.5) and (**F**) Seed (X 0.8) (Photographer Eng. Nabil Elmougi, the jojoba farms of The Egyptian Natural Oil Company, Ismailia Desert Road, Egypt). **Figure 1.** A photograph showing different organs of *Simmondsia chinensis*, (**A**) Branch of the plant (X 0.8), (**B**) Male flowers (X 1.0), (**C**) Old male and female trees (X 0.02), (**D**) Female flower (X 0.5), (**E**) Ripe fruit (X 0.5) and (**F**) Seed (X 0.8) (Photographer Eng. Nabil Elmougi, the jojoba farms of The Egyptian Natural Oil Company, Ismailia Desert Road, Egypt).

#### **3. Chemical Constituents 3. Chemical Constituents**

Jojoba oil is composed of almost 98% pure waxes (mainly wax esters, few free fatty acids, alcohols, and hydrocarbons), sterols, and vitamins with few triglyceride esters, so it is widely known as liquid wax rather than oil or fat [18]. Jojoba oil is composed of almost 98% pure waxes (mainly wax esters, few free fatty acids, alcohols, and hydrocarbons), sterols, and vitamins with few triglyceride esters, so it is widely known as liquid wax rather than oil or fat [18].

#### *3.1. Jojoba Wax 3.1. Jojoba Wax*

Investigation of the different organs of the jojoba plant for the presence of the wax revealed that the seeds contain most of the wax content in the plant (almost 50–52% of the seed weight) [5]. Jojoba wax is composed mainly of esters and, to a lesser extent, free acids, free alcohols, and hydrocarbons [4]. Esters are composed by the association of long straight-chain fatty acids with long straight-chain or higher molecular weight monohydric alcohols, C20 and C22; both the acids and alcohols are cis-monounsaturated at the (ω-9) position. Small triglyceride esters are also present [19–22]. Investigation of the different organs of the jojoba plant for the presence of the wax revealed that the seeds contain most of the wax content in the plant (almost 50–52% of the seed weight) [5]. Jojoba wax is composed mainly of esters and, to a lesser extent, free acids, free alcohols, and hydrocarbons [4]. Esters are composed by the association of long straight-chain fatty acids with long straight-chain or higher molecular weight monohydric alcohols, C20 and C22; both the acids and alcohols are cis-monounsaturated at the (ω-9) position. Small triglyceride esters are also present [19–22].

#### 3.1.1. Wax Esters 3.1.1. Wax Esters

The main components of the wax esters that have been isolated and previously identified are docosenyl eicosenoate "erucyl jojobenoate" (1), eicosenyl eicosenoate "jojobenyl jojobenoate" (2), eicosenyl docosenoate "jojobenyl erucate" (3), docosenyl docosenoate (4), eicosenyl oleate (5), and docosenyl oleate (6) (Table 1) [23]. Many other wax esters and free fatty alcohols and acids components are present in small quantities [19,24]. The main components of the wax esters that have been isolated and previously identified are docosenyl eicosenoate "erucyl jojobenoate" (1), eicosenyl eicosenoate "jojobenyl jojobenoate" (2), eicosenyl docosenoate "jojobenyl erucate" (3), docosenyl docosenoate (4), eicosenyl oleate (5), and docosenyl oleate (6) (Table 1) [23]. Many other wax esters and free fatty alcohols and acids components are present in small quantities [19,24].

It was initially thought that jojoba wax esters were made up of random combinations of alcohols and acids until Miwa conducted a study on these combinations [13]. He showed a significant difference between the observed results and those calculated by a It was initially thought that jojoba wax esters were made up of random combinations of alcohols and acids until Miwa conducted a study on these combinations [13]. He showed a significant difference between the observed results and those calculated by a random association of acids and alcohols. For instance, it was observed that (acid/alcohol, % experimental (% random)): (C20:1/C'20:1, 28.0% (31.8%)), (C20:1/C'22:1, 10.3% (5.7%)), (C22:1/C'20:1, 41.4% (32.0%)), (C22:1/C'22:1, 1.9% (5.7%)) indicating that eicosenyl do-

cosenoate ester is preferably biosynthesized by the association of eicosenoic acid and docosenol. These combinations demonstrate that plants favor specific associations, which correspond to their genome. From an analytical point of view, this observation constitutes a valuable tool for detecting adulterated oil and good discrimination between natural Jojoba wax and its synthetic substitutes. In the latter case, associations between fatty acids and alcohols are governed by thermodynamic rules, and random results would be observed. cosenol. These combinations demonstrate that plants favor specific associations, which correspond to their genome. From an analytical point of view, this observation constitutes a valuable tool for detecting adulterated oil and good discrimination between natural Jojoba wax and its synthetic substitutes. In the latter case, associations between fatty acids and alcohols are governed by thermodynamic rules, and random results would be observed.

random association of acids and alcohols. For instance, it was observed that (acid/alcohol, % experimental (% random)): (C20:1/C'20:1, 28.0% (31.8%)), (C20:1/C'22:1, 10.3% (5.7%)), (C22:1/C'20:1, 41.4% (32.0%)), (C22:1/C'22:1, 1.9% (5.7%)) indicating that eicosenyl docosenoate ester is preferably biosynthesized by the association of eicosenoic acid and do-

**Table 1.** Chemical structures for the most abundant wax ester components in jojoba wax. **Table 1.** Chemical structures for the most abundant wax ester components in jojoba wax.

*Polymers* **2021**, *13*, x FOR PEER REVIEW 4 of 22

3.1.2. Free Fatty Acids and Alcohols 3.1.2. Free Fatty Acids and Alcohols

It was reported that the natural oil contains small quantities of free fatty acids (0.96%) and free alcohols (1.11%), as seen in (Table 2) [13]. It was reported that the natural oil contains small quantities of free fatty acids (0.96%) and free alcohols (1.11%), as seen in (Table 2) [13].


**Table 2.** The composition of free fatty alcohols and fatty acids derived from jojoba oil. **Table 2.** The composition of free fatty alcohols and fatty acids derived from jojoba oil.

#### *3.2. Sterols*

 Tetracosenoic trace Tetracos-15-enoic 1.3 There are many reports concerning the sterol content of jojoba oil [5,19]. The major content of the sterols fraction is cholesterol (7), β-Sitosterol (8), campesterol (9), stigmasterol (10), and isofucosterol (11). Most of these sterols are sketched in Figure 2, and the composition is tabulated in Table 3 [22].

 Docos-13-enoic 13.6 Tricosenoic trace *3.2. Sterols* 

composition is tabulated in Table 3 [22].

**Figure 2.** Structures of major sterols content of jojoba oil. **Figure 2.** Structures of major sterols content of jojoba oil.



There are many reports concerning the sterol content of jojoba oil [5,19]. The major content of the sterols fraction is cholesterol (7), β-Sitosterol (8), campesterol (9), stigmasterol (10), and isofucosterol (11). Most of these sterols are sketched in Figure 2, and the
