Therapeutic Effects of Essential Oils: History
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EEssential oils (EOs) have been known for their therapeutic potential against many health issues. EOs may contribute to the regulation and modulation of various biomarkers and cellular pathways responsible for metabolic health as well as the development of many diseases, including cancer, obesity, diabetes, cardiovascular diseases, and bacterial infections. 

  • essential oils
  • anti-inflammatory
  • anti-cancer
  • metabolic health

1. Antioxidant, Anti-Inflammatory, and Anti-Cancer Activities of Essential Oils

Recent cumulative research suggests that EOs exhibit anti-inflammatory, antioxidant, and anticancer properties in cell and animal models [3,29,30]. Inflammation is a normal response to tissue damage caused by stimuli that could be biological, chemical, or physical [31]. EOs decrease the prerequisite compounds that exaggerate the inflammation process, namely, reactive oxygen species (ROS) and nitrogen species, NF-κB, and proinflammatory cytokines [32]. A comprehensive review of EOs revealed that oils extracted from lemon (Citrus Limon) fruit peels and leaves exerted antioxidant and radical scavenging activities under in vitro conditions [33]. Moreover, it was observed that the monoterpene hydrocarbon fraction was positively correlated with antioxidant activity [33]. Citrus EOs, namely, mandarin, wilking, and clementine, exhibited antioxidant activity by acting as free radical scavengers in a dose-dependent manner [34]. Edema is a pathological feature of inflammation [35]. Carrageenan, a pro-inflammatory agent, was used to induce paw edema in rats, while bergamot EO was applied for its anti-inflammatory effect. It was observed that the bergamot EO significantly decreased the inflammatory markers, namely, prostaglandin (PGE2) and nitrite/nitrate levels, as well as interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF-α) [35]. On a similar note, sesame seed oil decreased lipid peroxidation and nitric oxide production besides increasing antioxidant enzymes such as superoxide dismutase (SOD), glutathione (GSH), GSH peroxidase (GPx), and catalase (CAT) by binding the fatty acids in sesame seed with COX-2 and PGE2 [36]. The COX-2 enzyme activates pain (a symptom of inflammation) mechanisms in the human body. The phytochemical components inherent to sesame seed oil, like sesamol, sesamin, and sesamolin, are responsible for their antioxidant and anti-inflammatory properties [37]. A clinical trial was conducted to investigate the effect of sesame oil on 40 hypertensive male and female patients aged 35–60 years [38]. The results demonstrated that sesame EO decreased lipid peroxidation and increased antioxidant activity [38]. Likewise, eugenol—a bioactive compound in clove EO—decreased rat paw swelling and synovial immune cell infiltration [39]. EOs of the oregano flowering plant (O. vulgare) have also been recognized for their antioxidant potential [40,41]. In contrast, it was also observed that bergamot EO increased intracellular ROS production induced by N-formyl-Met-Leu-Phe in the presence of extracellular Ca2+ chelators. Thereby, the pro-inflammatory potential of EOs also needs to be carefully considered for any future clinical applications [42].
Cancer may significantly increase the fatality rate of the disease by compromising the immune system. The abundant bioactive components in EO may offer immune-boosting activity in the treatment of cancer [43]. Navel orange EO exhibited good anti-cancer potential against lung cancer and prostate cancer [44]. Similarly, non-volatile fractions of bergamot EO, such as coumarins and furocoumarins, showed anti-mutagenic activity [45]. EOs from Croton flavens leaf were observed to be effective on human lung carcinoma and human colon adenocarcinoma cell lines, respectively [46]. Another study identified that an EO from Curcumae rhizoma (CR) inhibited the growth of colon cancer by improving tumor vessel structure, reducing angiogenesis in tumors, and normalizing tumor vessels in both in vitro and in vivo models [47]. Similarly, a recent study demonstrated that oregano EO-based nanoemulsion increased prostate cancer cell death through apoptosis and decreased lipid droplet accumulation via targeting HMGCR, FASN, and SREPB1 signals in vitro [48].
The ability of the EOs to exhibit these bioactive properties could be attributed to their composition of terpenes, hydrocarbons, alcohols, aldehydes, ketones, and esters [49,50,51]. Usually, the method of extraction used to obtain the EO is determined according to the purpose of use. Due to the lipophilic nature of EOs and their low molecular weight, they can easily cross cell membranes or even alter the membrane composition and increase/decrease membrane fluidity [52]. Consequently, changes within the membrane structure lead to the leakage of ions and cytoplasmic molecules, reduced ATP production, and loss of mitochondrial potential, eventually resulting in cell death [53]. Moreover, EOs, upon entering the cell membrane, activate apoptosis and necrosis pathways, resulting in cell death, cell cycle arrest, and loss of function of essential organelles [53]. EOs encourage the condensation and fragmentation of nuclei and chromatin, causing a loss of cristae in the mitochondria, which eventually leads to cell apoptosis [54]. In conclusion, EOs may reduce inflammation, oxidative stress, and cancer development through targeted actions both at the physiological and cellular levels, which are summarized in Figure 2.
Figure 2. Targeted actions of EOs for the reduction of inflammation and cancer.

2. EOs: A Remedy for the Management of Metabolic Syndrome

Metabolic syndrome (MetS) is a group of risk factors that predispose an individual to cardiovascular disease and type II diabetes mellitus of metabolic origin. Typical MetS risk factors include obesity, high blood pressure, high blood sugar, and dyslipidemia (high triglycerides and/or low high-density lipoprotein cholesterol) [55]. The pathophysiology and the exact etiology of the development of MetS are not very clear [56]. However, MetS has been associated with increased oxidative stress [57] and is characterized by elevated inflammatory markers [58]. Furthermore, obesity and insulin resistance lead to an increase in proinflammatory cytokines such as TNF-α and IL-6.

2.1. EOs and Obesity

Obesity could be classified as the primary initiating factor of MetS, and attaining a healthy body weight is one of the first lines of treatment. Multiple plant-derived EOs, which are rich sources of volatile organic compounds, have long been used for the complementary treatment of obesity [59]. Several in vitro and in vivo studies suggest that the anti-obesity effects of EOs are achieved by the down-regulation of adipogenic transcription factors such as PPARγ and CEBPα at both protein and mRNA levels, the elevation of the plasma glycerol concentration (a marker of lipolysis), as well as the suppression of fat accumulation and intracellular triglycerides [60]. The EOs from the Citrus family have been widely investigated for their anti-obesity properties [60]. In an animal study, sweet orange EO was suggested as a potential dietary supplement for weight loss, since it decreased the expression of peroxisome proliferators-activated receptor-γ (PPARγ), upregulated uncoupling protein 2 (UCP-2), hormone-sensitive lipase (HSL) and carnitine palmitoyltransferase I (CPT-I), and inhibited the expression of acetyl-CoA carboxylase (AAC) [61]. The bioactive compound (+)-limonene, extracted from citrus peel EO, exhibited anti-obesity properties [62]. Moreover, grapefruit and citrus EOs are commonly used in aromatherapy for weight loss programs [63,64].

2.2. EOs and Diabetes

Diabetes is a common complication of MetS. It is important to note that EOs may help in the management of diabetes mellitus (DM), but they cannot be used as a cure. The EOs exhibit their antidiabetic action by inhibiting α-amylase and α-glucosidase enzymes, and by increasing insulin sensitivity or/and insulin secretion [65]. EOs can also be used to reduce common complications of diabetes, such as ulcers and loss of skin integrity, and can decrease the duration of the infection [66]. EOs from Asian ginseng (Panax quinquefolius), fenugreek (Trigonella foenum-graecum), and aloe (Aloe vera) have been observed to improve glucose tolerance [67]. Lavender EO (Lavandula stoechas L.) was protective against diabetes and decreased the associated renal and hepatic injuries in diabetic rats [68]. A mixture of cinnamon bark (Cinnamomum zeylanicum), cumin (Cuminum cyminum), fenugreek (Trigonella foenum-graecum), and oregano (Origanum vulgare) was observed to lower glucose levels by enhancing insulin sensitivity [69]. One animal study suggested that bioactive compounds in cinnamon (Cinnamomum veru) can regulate adipocyte gene expression to improve glucose transport and insulin signaling [70]. Under in vitro conditions, hydro-distilled EO from clove buds inhibited the activities of α-amylase and α -glucosidase [71]. However, a meta-analysis identified only one randomized controlled study on the impact of EO on diabetes and thereby, a conclusive statement that provides evidence-based health claims on this issue cannot be made [72].

2.3. EOs and Hypertension

Hypertension is another hallmark risk factor for the development of MetS. Antihypertensive medications and lifestyle modifications are the primary treatments for hypertension [73]. Preliminary studies indicate that EOs are effective in decreasing blood pressure and heart rate [74,75]. Ref. [74] blended four EOs, namely lavender (Lavandula officinalis), ylang-ylang (Cananga odorata), marjoram (Origanum majorana), and neroli (Citrus aurantium). The immediate and long-term effects of the EOs were evaluated by monitoring the 24-h ambulatory blood pressure and salivary cortisol levels, respectively. It was observed that the EO blend significantly decreased the daytime blood pressure and salivary cortisol concentration. However, there was an insignificant decrease in nighttime blood pressure [74]. Carvacrol, the major component of oregano EO, may help decrease blood pressure as it causes peripheral vasodilatation and inhibits the contraction elicited by intracellular Ca2+ influx through CAV (voltage-dependent calcium) channels and transient receptor potential (TRP) channels [76,77,78,79]. A systematic review indicated no significant effect of inhaled EOs on blood pressure reduction in patients with hypertension [80].

2.4. EO and Dyslipidemia

Dyslipidemia is one of the major contributors to MetS. Lemon balm EO (Melissa officinalis) decreased triglycerides and reduced the expression of genes involved in fatty acid synthesis [74]. The purple yam (Dioscorea alata L.) was reported to be effective in controlling adipose tissue mass and increasing high-density lipoprotein cholesterol (HDL-C), decreasing triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) concentrations associated with gut microbiota modulation [81]. The antihyperlipidemic effect of EOs could be due to their ability to activate lipoprotein lipase [65].
Interestingly, some studies investigated the impact of EOs on two or more risk factors for MetS rather than concentrating only on one risk factor. Cinnamon extracts (Cinnamomum veru) exhibited antidiabetic properties and had a beneficial impact on lipid profiles [82,83,84]. Hedge nettles from the Stachys species, commonly referred to as “mountain tea” are consumed in various parts of the world as a herbal tea to treat different medical conditions [85]. The bioactive compounds in this tea include germacrene D, β-pinene, α-pinene, hexahydrofarnesyl acetone, and valeranone. These compounds were observed to play a role in glucose homeostasis and prevent the absorption of fats by inhibiting enzymes such as cholinesterases, glucosidase, amylase, tyrosinase, and lipases respectively [86]. Similarly, lemon balm extract also prevented or concomitantly treated DM-associated dyslipidemia and hypercholesterolemia [87].

2.5. Dosage, Bioactive Metabolites, Therapeutic, and Adverse Effects of EOs

The researchers have reviewed the therapeutic effects, dosage, and possible side effects of EOs extracted from different sources such as peppermint, chamomile, fennel, rosemary, fenugreek, garlic, cumin, and lavender, among others, against various diseases, including microbial infections, obesity, diabetes, hypertension, and dyslipidemia (Table 1). Previous studies suggested that 225 mg/day of peppermint EOs may reduce the microbial dysbiosis and the total symptom score in patients with IBS [88,89,90]. Consumption of 100 mg/kg/b.w of chamomile EO prevents obesity and dyslipidemia, by reducing the weight gain and improve the lipid profile, and kidney and liver functions in animal models [91]. In addition, 3 g of chamomile EOs decreased the HOMA-IR index, serum HbA1C, TAG, TC, and LDL levels in patients with type 2 diabetes [92,93,94,95]. The use of 15 mg/kg/b.w and 7.5 mg/kg of fennel and rosemary EOs confer protection against hypertension and improve cardiac and renal function through anti-inflammatory and antioxidant activities [96,97]. Moreover, the consumption of 50 mg/kg/b.w of garlic EOs exerted anti-obesity and anti-hyperlipidemic effects by reducing HFD-induced body weight gain and adipose tissue weight [98,99]. The bioactive ingredients responsible for the therapeutic effects of EOs are polyphenols, flavonoids, tocopherols, menthone, tanins, luteolin, apigenin, transanethole, terpenoids, estragole, fenchone, limonene, diallyl disulfide, cuminaldehyde, α-pinene, γ-terpinene, linalool, and linalyl acetate [88,89,90,91,92,93,94,95,96,97,98,99,100,101,102]. The majority of these bioactive components have strong antioxidant activities, like phenolic compounds, terpenoids, luteolin, apigenin, estragole, fenchone, and limonene [91,92,93,94,95,101,102]. On the other hand, there are some side effects associated with the consumption of EOs. Therefore, it is important to know about the possible effects of EOs before using them. Previous studies demonstrated that EOs act as an endocrine disrupting chemical (EDC), an exogenous agent that interferes with hormonal release, action, storage, and metabolism in the body. However, EO may act as an agonist to the estrogen receptor alpha (ERα),antagonist to the androgen receptor (AR), and may cause endocrine disruption [103]. Regular exposure to lavender and tea tree oil is associated with abnormal breast growth and premature gynecomastia in adolescents [104,105]. Mild skin irritation was associated with consumption of chamomile tea in patients with type 2 DM [92].
Table 1. Dosage, bioactive metabolites, therapeutic, and adverse effects of EOs.

3. Enhance Breast Milk Production and Childcare

Breastfeeding is beneficial for both mother and child from an immunological, physiological, psychological, and nutritional perspective [106,107]. However, poor milk production is considered one of the most common issues leading to early cessation of breastfeeding. Factors such as cesarean delivery, preterm birth, pain, fatigue, anxiety, return to work, emotional stress, and postpartum depression may affect milk production [108,109].
Medical and herbal galactagogues are often used to augment and increase milk production [110,111,112]. Nonetheless, aromatherapy accompanied by massage has been used historically as an alternative therapy [113,114]. Previous literature suggests that lavender oil has a comforting effect on the central nervous system, and a massage with lavender oil can increase milk production and prolactin levels in mothers [115,116,117]. A combination of aromatherapy and massage using EOs increased milk production to a larger extent, as compared to individual treatments [118]. Similarly, jasmine oil has been observed to increase milk secretion [119]. Furthermore, the application of menthol essence and peppermint is effective against nipple fissures common in lactating mothers [120,121].
EOs have also been observed to be beneficial during pregnancy and labor. Lemon EO (citrus lemon) effectively reduced nausea and vomiting during pregnancy [122]. Additionally, a randomized controlled trial observed that lavender aromatherapy massages helped reduce pain and the duration of labor [123]. Moreover, a triple-blind, randomized, placebo-controlled trial revealed that inhaling lavender essence may help decrease pain after a Caesarean section when used along with other medical and therapeutic approaches [124].
Literature reveals that EOs are also beneficial for infants and children. In one study, massaging with lavender oil was effective in relieving infants of the symptoms of colic [125]. During bathing, adding lavender oil reduced stress and crying and enhanced sleep in very young infants [126]. Using lavender aromatherapy during dental treatment decreased children’s anxiety and perception of pain [127]. Lavender oil was also effective in alleviating pain during blood sampling and vaccinations in children [128]. Similar results were shown in decreasing anxiety in children with diabetes using orange oil aromatherapy [129]. Aromatherapy using Rosa damascena EO showed improved sleeping quality in children with sleep disorders [130]. Moreover, EOs decreased chemotherapy-induced nausea and vomiting, decreased distress in burn patients, and the prevalence of rhinitis symptoms in children [131,132,133].

4. EOs: Natural Antibiotics

Foodborne pathogens are a common cause of foodborne illnesses that affect millions of people every year, sometimes with severe and lethal consequences [134]. As commonly used food preservatives are chemical in nature and may only be added up to a certain degree to prevent changes in taste/odor, there is a fair demand to identify naturally sourced compounds that would exert a similar effect without altering the organoleptic properties negatively [135]. Previously, extensive investigation into the use of EOs as food preservatives in the food industry has been conducted [52]. EOs have been observed to be effective against both pathogenic and non-pathogenic organisms [136,137,138,139,140,141]. They have been observed to be effective against gram-positive (Staphylococcus aureus and Listeria monocytogenes) and gram-negative bacteria (Escherichia coli and Salmonella enteritidis) [142]. Several studies conducted on food materials reported bactericidal or bacteriostatic activity of EOs against Salmonella enterica, Escherichia coli O157:H7, Staphylococcus aureus, Listeria monocytogenes, Lactobacillus plantarum, Saccharomyces cerevisiae, and Candida albicans strains [140,141,143,144]. Three citrus fruit EOs, mandarin (Citrus reticulata), wilking (Citrus reticulata cv. Wilking blanco), and clementine (Citrus clementina), were examined for their antimicrobial potential. Mandarin EO demonstrated the best bacterial growth inhibition, followed by clementine EOs [34]. The oils were significantly effective against Candida albicans, Escherichia coli, Listeria innocua, methicillin-resistant S. aureus, and Staphylococcus aureus [34]. Clove and melaleuca EO showed an inhibitory effect on S. aureus, E. coli, and C. albicans [145].
Phenolic EOs such as carvacrol, thymol, and others consist of hydrophobic ends that interact with different areas of microbial cells (e.g., cell wall and cytoplasmic membrane) and break the membrane structure, thereby causing a loss of cellular constituents and resulting in cell death [146].

5. Other Beneficial Effects of EOs

Mixtures containing the EOs of sage, oregano [147], J. oxycedrus subsp. oxycedrus, and J. phoenicea [148], have been reported to encourage wound healing. Similarly, a combination of sesame and lemon EOs accelerated the healing process of wounds in male Albino Wistar rats [149]. EOs have also been observed to cause subtle ST-segment elevation and decrease the levels of malondialdehyde and myeloperoxidase in rat models that had been induced with a myocardial infarction [150]. Malondialdehyde and myeloperoxidase are the markers that indicate necrosis of the myocardium; thus, the ability of EOs to reduce the levels of these enzymes points towards better heart health. Previous studies have also observed the positive effects of EOs on hepatic function. EOs of rosemary (Rosmarinus officinalis L.) and fennel (Foeniculum vulgare) have been associated with decreasing the levels of alanine aminotransferase (ALT) and alkaline phosphatase (ALP) [151,152]. These biomarkers indicate liver function insufficiency/damage. Acetominophen toxicity accounts for 50% of overdose-related acute liver failure and approximately 20% of liver transplant cases in the United States. EOs have also aided in treating such cases. EO extracted from Nepeta cataria L. increased the mRNA expression of uridine diphosphate glucuronosyltransferases and sulfotransferases [153]. These enzymes aid in metabolizing acetominophen into a nontoxic form that can be excreted through urine.
The beneficial effect of EOs on brain health has also been observed. Rosemary EO enhanced memory, concentration, alertness, and locomotor activity, besides stimulating the cerebral cortex and causing mood relaxation [154]. EOs from sage, rosemary, and Stachys inflata Benth inhibited acetylcholine esterase (AChE) even better than the drug donepezil [86,155]. This is a significant observation, especially for Alzheimer’s disease patients, as elevated activity of the enzyme (AChE) has been associated with the disease. The inhibitory potential of the AChE enzyme has been associated with the di- and triterpenes present in the EOs [155].
EOs have also been shown to exert beneficial effects on asthmatic patients; eucalyptol extracted from eucalyptus oil reduced the dependence on oral steroids by such patients [156]. Their usage has also been observed to reduce symptoms associated with primary dysmenorrhea [157] and labor pain [158]. Other benefits recorded include the ability to inhibit tyrosinase (anti-hyperpigmentation effect) [86], elastase (anti-wrinkle effect) [159], anti-viral [160], and anti-fungal activity [159,160]. Overall, EOs may positively change the course of many health issues, including obesity, dyslipidemia, hypertension, diabetes, and infections, along with improvements in brain, heart, and liver health (Figure 3).
Figure 3. Sources of EOs and their respective health-promoting properties.

This entry is adapted from the peer-reviewed paper 10.3390/molecules28041809

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