Volatile Oils: Limonene and Humulene

Volatile Oils

• Hydrocarbon Volatile Oils

  • Lemon peel (Synonym: limon)
    • Origin: outer rind of fresh ripe Citrus limon fruit (Rutaceae).
    • Constituents: terpene (limonene), aldehyde, volatile oil, coumarins, flavonoids (rutin, hesperidin)
    • Research shows limonene has significant antioxidant and cytotoxic activity in mouse leukemia cells, impacting cells via necrosis and apoptosis.
  • Types of Hydrocarbons:
    • Monocyclic (e.g., limonene in citrus)
    • Dicyclic (e.g., Pinene)
    • Acyclic (e.g., Myrcene)
    • Sesquiterpene (e.g., Cadinene)
  • Limonene: Further studies show anti-tumorigenic effects against pancreatic and breast cancer. Limonene exhibits antioxidant, radical scavenging, and cytotoxic activity in several model systems for those cancers. It has strong anti-inflammatory, antiproliferative, and anti-invasive activities along with potential anti-angiogenic effects.

• Humulene:

  • A naturally occurring monocyclic sesquiterpene from Humulus lupulus Cannabinaceae.
  • Shown to produce anti-inflammatory effects, potentially valuable in managing inflammatory diseases.
  • Similar effects to dexamethasone; reduces edema formation caused by histamine injections.
  • Inhibits tumor necrosis factor-α (TNF-α) and interleukin-1β.

• Kaurene:

  • A diterpene found in Agathis plants.
  • Exhibits potent anti-tumor activity by inhibiting cell proliferation.

• Oil of Turpentine (Synonym: spirit of turpentine, rectified oil of turpentine)

  • Origin: rectified volatile oil distilled from the oleoresin of Pinus palustris (Pinaceae).
  • Constituents: α- and β-pinene, camphene
  • Primarily used as an external counterirritant, rubifacient, fragrance, and flavoring agent.
  • Rectified turpentine oil:
    • Derived from Humulus lupulus (Cannabinaceae)
    • Consists of β-myrcene
    • Used as a local irritant, expectorant, diuretic, and urinary antiseptic

• Alcoholic Volatile Oils

  • Acyclic Alcohols:
    • Methyl, ethyl, isobutyl, isoamyl, hexyl, and higher aliphatic alcohols are present, typically removed during steam distillation due to water solubility.
  • Monocyclic Alcohols:
    • Menthol, a key example
  • Bicyclic Alcohols:
    • Borneol, a bicyclic terpene

• Sesquiterpene Alcohols:

  • Includes zingiberol, found in Zingiber officinale.
  • Used as an antiemetic, carminative, and in treating hyperemesis gravidarum as well as postoperative nausea and vomiting
  • Possesses cardio vascular properties mainly due to the inhibition of prostaglandin synthetase; also inhibits thromboxane synthesis, and lowers cholesterol levels. It has antifungal, antibacterial and anthelmintic properties.

• Peppermint Oil

  • Origin: dried leaves of Mentha piperita (Labiatae)
  • Constituents: menthol, pinene, limonene, resin, tannin
  • Uses: pharmaceutical aid (flavor enhancer), carminative, stimulant, counterirritant, antibacterial, antiviral, antispasmodic, and anti-flatulence.
  • Menthol has cytotoxic effects on murine leukemia cells in a concentration-dependent manner. Menthol inhibits topoisomerase I and II, impacting prostate and bladder cancer cells and reducing their invasive potential.

• Adverse Effects (Menthol):

  • Gallstones, obstructed bile ducts, gall bladder inflammation and severe liver damage.
  • Skin irritation in burns and sunburns
  • Internal use can be a depressant to the heart.

• Biosynthesis of Menthol Pathway: Neryl p.p. → Terpineol → Terpinolene → Piperitone → Menthone → Menthol

• Key step in menthol biosynthesis: Dehydration of Terpineol to Terpinolene, a reaction where NADPH2 is an essential cofactor in the reduction reaction.

• Menthol exists as levo(-) (from natural sources) and racemic (+) (synthetic) forms.

• Ketone Volatile Oils

  • Monocyclic: Menthone, Carvone, Pulegone
  • Di/Bicyclic: Camphor
  • Non-Terpenic:
  • Important drugs are Camphor, Spearmint, and Caraway

• Camphor:

  • Origin: Cinnamomum camphora (Lauraceae), occurs as crystalline product in clefts of the wood of the plant.
  • Biosynthesis: Geranyl pyrophosphate → Linaloyl pyrophosphate→ Bornyl pyrophosphate → Borneol → Camphor
  • Properties: readily absorbed through skin, creates cooling sensation (similar to menthol), local anesthetic and antimicrobial, anti-itch. Used topically to increase blood flow and as a counter-irritant, reducing pain and swelling by causing irritation. It is important to avoid broken skin because camphor can quickly absorb into the body and potentially cause poisoning due to high concentration.

• Spearmint:

  • Origin: Mentha spicata (Labiatae)
  • Constituents: (-) carvone, (-) limonene, phellandrene
  • Use: carminative, stimulant, flavoring agent.

• Dill:

  • Origin: Anethum graveolens (Apiaceae)
  • Constituents: carvone, limonene
  • Use: carminative, flavoring agent, infant's gripe water, antispasmodic, bacteriostatic, calming effect, menstrual cycle regulation.

• Aldehyde Volatile Oils:

  • Acyclic: Citral (cinnamal)
  • Cyclic: Aromatic (cinnamon oil)
  • Aldehyde oils have a calming effect on the nervous system, reducing stress.

• Cinnamon:

  • Origin: Dried bark of Cinnamomum verum (Lauraceae)
  • Constituents: Cinnamaldehyde (major compound)
  • Benefits: regulates blood sugar levels, reduces cholesterol levels, aids digestion, relieves sinus congestion, joint pain, muscle stiffness, reduces inflammation and arthritis pain, prevents tooth decay, improves circulation, relieves menstruation cramps.

• Phenolic Volatile Oils (Thyme)

  • Origin: Dried leaves and flower tops of Thymus vulgaris (Labiatae)
  • Constituents: Thymol, carvacrol
  • Thymol is a powerful antibacterial and antiseptic agent, effective against various bacteria (E. coli, Pseudomonas aerogenosa, Staphyllococcus aureus, and Bacillus), and also has significant antifungal activity across different fungi. Thymol benefits in reducing bloating spasms, boosting appetite and treating candidiasis, gastroenteritis and digestive tract issues.

• Clove Oil:

  • Origin: Dried flower buds of Eugenia caryophyllus (Myrtaceae)
  • Constituents: Eugenol, gallotannic acid, oleanolic acid, vanillin, chromone, eugenin
  • Use: flavoring, stimulant, aromatic, antiseptic, dental analgesic, and antibacterial agent.

• Phenolic Ether Volatile Oils (Anise)

  • Origin: Dried ripe fruits of Pimpinella anisum (Apiaceae)
  • Constituents: Anethole, methyl chavicol, pinene, linalool, anisaldehyde
  • Use: flavoring, aromatic stimulant, carminative. Anethole is a colorless or pale yellow liquid that solidifies to a crystalline mass at lower temperatures. It has a sweet taste and aroma of anise..

• Nutmeg:

  • Origin: Dried kernels of Myristica fragrans (Myristicaceae)
  • Constituents: Myristicin, safrole, eugenol
  • Use: flavoring agent, carminative, condiment, traditional medicine (infantile diarrhea). Nutmeg has psychoactive and hallucinogenic properties; however, excessive consumption can lead to adverse effects like skin flushing, tachycardia, and reduced saliva production.

• Oxide Volatile Oils (Eucalyptus)

  • Origin: Dried leaves of Eucalyptus globulus (Myrtaceae)
  • Constituents: 1,4-Cineole, 1,8-Cineole, resins, tannic acid
  • Properties: Fresh camphor-like smell, spicy and cooling taste; insoluble in water but miscible with ether and ethanol, boiling point reaches 176°C. Eucalyptol forms crystalline adducts with hydrohalic acids and phosphoric acid which aids in purification processes.
  • Use: Pleasant aroma and taste, used in flavorings, fragrances and certain cosmetics. It can also be a flavoring agent at low levels, used for mouthwash and cough suppressants.

• Ester Volatile Oils (Wintergreen Oil)

  • Origin: Gaultheria procumbens (Ericaceae)
  • Constituents: Methyl salicylate
  • Use: Topical treatment (diluted) for muscle aches, arthritis, edema, poor circulation, headaches, inflammation, eczema, psoraisis, gout, ulcers; aroma therapeutic uses; added to toothpaste, chewing gum, and soft drinks.
  • Risks of excessive consumption are similar to aspirin.