Sweet Orange (Peel) — Citrus × sinensis (L.) Osbeck (peel)

Sweet Orange (Peel) — Citrus × sinensis (L.) Osbeck (peel)

Product Name: Апельсин сладкий, Citrus × sinensis (L.) Osbeck, Apfelsine, Naranja dulce, Oranger doux, البرتقال الحلو, ส้มสุก, Apelsin, Апельсин, Portağal, Апельсин, Apelsinas, Apelsīns, Апельсин, תפוז מתוק

Synonyms: апельсин, оранжевое дерево, померанец, sweet orange, orange tree, Apfelsinenbaum, süße Orange, naranjo dulce, arbre d’orange, oranger, البرتقال, شجرة البرتقال, ส้มโอ, ส้มเทศ

Used Parts: Flowers, leaves, shoots, peel, seeds, pulp, juice, roots

Main Indications for Use of Sweet Orange (Citrus × sinensis): Dyslipidemia, obesity, type 2 diabetes mellitus, chronic gastritis, functional dyspepsia, irritable bowel syndrome, hypertension, atherosclerosis, chronic ischemic heart disease, acute bronchitis, chronic bronchitis, acute respiratory viral infections, influenza, iron deficiency anemia, chronic cholecystitis, fatty liver disease, chronic pancreatitis, dermatophytosis, mucosal candidiasis, herpesvirus infection, depressive disorder, anxiety disorder, insomnia.

Use of Sweet Orange (Citrus × sinensis) in Mixtures and Complexes: Chronic pyelonephritis, urolithiasis, acute and chronic sinusitis, allergic rhinitis, psoriasis, atopic dermatitis, rheumatoid arthritis, osteoarthritis, spinal osteochondrosis, chronic venous insufficiency, varicose veins, hemorrhoids, chronic obstructive pulmonary disease, pulmonary tuberculosis, chronic hepatitis, viral hepatitis B and C, gastrointestinal oncological diseases, benign neoplasms of the female reproductive system.

Pharmacological Properties of Sweet Orange (Citrus × sinensis): Antioxidant, anti-inflammatory, hypolipidemic, hypoglycemic, antimicrobial, antiviral, fungicidal, spasmolytic, cardioprotective, hypotensive, immunomodulatory, choleretic, hepatoprotective, sedative, anxiolytic, adaptogenic, antitumor, wound healing, tonic, analgesic, anti-edematous, diuretic, antiplatelet, photoprotective.

Dosage of Pharmaceutical Forms — Sweet Orange (Citrus × sinensis)

Powder — Sweet Orange (Citrus × sinensis)

Indications (Powder): Dyslipidemia, obesity, type 2 diabetes mellitus, chronic gastritis, functional dyspepsia, irritable bowel syndrome, hypertension, atherosclerosis, chronic ischemic heart disease, acute bronchitis, chronic bronchitis, acute respiratory viral infections, iron deficiency anemia, chronic cholecystitis, fatty liver disease, chronic pancreatitis, mucosal candidiasis, herpesvirus infection.

Standard Dosage (Powder): 2-4 grams of powder per day, divided into 2 doses, taken orally after meals with warm water.

Enhanced Dosage (Powder): 5-6 grams per day for atherosclerosis, obesity, type 2 diabetes mellitus, chronic pancreatitis — under medical supervision.

Maximum Dosage (Powder): 8 grams per day for severe hyperlipidemia and metabolic syndrome, course not exceeding 14 days.

Preventive Dosage (Powder): 1-2 grams per day, in courses of 20 days, 2-3 times a year for chronic ischemic heart disease, stage I hypertension, chronic gastritis in remission, chronic cholecystitis in remission.

Pediatric Dosage (Powder): from 6 years old, body weight from 20 kg — 0.5-1 gram per day; from 12 years old — 1-2 grams per day.

Contraindications (Powder): allergy to citrus fruits, peptic ulcer disease of the stomach and duodenum in the acute phase, gastritis with high acidity; data on contraindications during pregnancy, lactation, and in children under 6 years old are not scientifically registered.

Side Effects (Powder): with overdose — nausea, heartburn, diarrhea, increased gastralgia.

Adjustment for Patient Body Weight: For body weight less than 60 kg — reduce the dose by 20%; for body weight over 90 kg — increase the dose by 10%.

Preparation method (Powder): Ingredients for 100 g: Sweet orange peel — 100 g (fresh weight recalculated to dry weight).

• Rinse the raw material thoroughly, remove any remaining pulp.
• Cut into strips 2-3 mm thick.
• Dry in a drying cabinet at a temperature of 40°C until constant weight is achieved.
• Grind into powder in a mill to a particle size of no more than 0.3 mm.
• Sift through a sieve.
• Package in an airtight container.

Storage Conditions and Shelf Life (Powder): Store in a dry, light-protected place, at a temperature of 5 to 25°C, relative humidity not exceeding 60%, away from direct sunlight and sources of electromagnetic radiation. Shelf life — 12 months. After opening the package, use within 60 days.

Dry Extract — Sweet Orange (Citrus × sinensis)

Indications (Dry Extract): Dyslipidemia, obesity, type 2 diabetes mellitus, chronic gastritis, functional dyspepsia, irritable bowel syndrome, hypertension, atherosclerosis, chronic ischemic heart disease, acute and chronic bronchitis, acute respiratory viral infections, fatty liver disease, chronic pancreatitis, mucosal candidiasis, herpesvirus infection, depressive disorder, anxiety disorder.

Standard Dosage (Dry Extract): 300-500 mg of dry extract (in terms of 100% dry matter) twice daily, taken orally after meals.

Enhanced Dosage (Dry Extract): 600-800 mg twice daily for obesity, metabolic syndrome, severe hyperlipidemia.

Maximum Dosage (Dry Extract): 1000 mg twice daily for severe hyperlipidemia — course not exceeding 4 weeks.

Preventive Dosage (Dry Extract): 250 mg once daily in courses of 30 days twice a year for chronic ischemic heart disease, stage I hypertension, chronic gastritis in remission.

Pediatric Dosage (Dry Extract): from 12 years old, body weight from 40 kg — 150-250 mg per day; under 12 years old — no data.

Contraindications (Dry Extract): allergy to citrus fruits, peptic ulcer disease of the stomach and duodenum in the acute phase, gastritis with high acidity; data on contraindications during pregnancy, lactation, and in children under 12 years old are not scientifically registered.

Side Effects (Dry Extract): with overdose — nausea, heartburn, diarrhea, headache, insomnia.

Adjustment for Patient Body Weight: For body weight less than 60 kg — reduce the dose by 20%; for body weight over 90 kg — increase the dose by 10%.

Preparation method (Dry Extract): Ingredients for 100 g of finished extract: Dry sweet orange peel — 500 g, 70% ethanol (organic solvent) — 2.5 L.

• Grind the raw material to particles of 3-5 mm.
• Place in an extractor, add ethanol.
• Macerate for 7 days at room temperature, stirring daily.
• Filter.
• Remove the solvent by evaporation in a water bath at a temperature not exceeding 50°C to obtain a thick residue (control — complete disappearance of ethanol odor).
• Dry the residue in a vacuum drying cabinet at 40°C to a powdery state.
• Package in an airtight container. Permissible residual ethanol content in the finished extract — not more than 500 ppm.

Storage Conditions and Shelf Life (Dry Extract): Store in a dry, light-protected place, at a temperature of 5 to 25°C, relative humidity not exceeding 60%, away from direct sunlight and sources of electromagnetic radiation. Shelf life — 24 months. After opening the package, use within 90 days.

Tincture — Sweet Orange (Citrus × sinensis)

Indications (Tincture): Dyslipidemia, obesity, type 2 diabetes mellitus, chronic gastritis with low acidity, functional dyspepsia, irritable bowel syndrome, hypertension, atherosclerosis, chronic ischemic heart disease, acute and chronic bronchitis, acute respiratory viral infections, fatty liver disease, chronic pancreatitis, mucosal candidiasis, herpesvirus infection, anxiety disorder, insomnia.

Standard Dosage (Tincture): 20-30 drops (1-1.5 ml) 2-3 times daily, diluted in 50 ml of warm water, taken orally 30 minutes before meals.

Enhanced Dosage (Tincture): 40 drops (2 ml) 3 times daily for obesity, atherosclerosis, chronic ischemic heart disease — course up to 21 days.

Maximum Dosage (Tincture): 50 drops (2.5 ml) 3 times daily for severe hyperlipidemia, fatty liver disease, metabolic syndrome, course not exceeding 14 days.

Preventive Dosage (Tincture): 15-20 drops (0.75-1 ml) once daily in a course of 20 days, twice a year for chronic ischemic heart disease, stage I hypertension, chronic gastritis in remission.

Pediatric Dosage (Tincture): from 12 years old, body weight from 40 kg — 5-10 drops 1-2 times daily, diluted in water; under 12 years old — no data.

Contraindications (Tincture): allergy to citrus fruits, peptic ulcer disease of the stomach and duodenum in the acute phase, gastritis with high acidity, liver diseases in the stage of decompensation; data on contraindications during pregnancy, lactation, and in children under 12 years old are not scientifically registered.

Side Effects (Tincture): with overdose — nausea, heartburn, palpitations, insomnia.

Adjustment for Patient Body Weight: For body weight less than 60 kg — reduce the dose by 20%; for body weight over 90 kg — increase the dose by 10%.

Preparation method (Tincture): Ingredients for 100 g of finished tincture: Dry sweet orange peel — 20 g, 40% ethanol (organic solvent) — 80 ml.

• Grind the raw material to particles of 3-5 mm.
• Place in a glass container, add ethanol.
• Close tightly, macerate for 14 days at room temperature, shaking daily.
• Filter through gauze.
• If necessary, remove part of the ethanol by evaporation in a water bath at a temperature not exceeding 50°C (to achieve the required solution strength).
• Permissible residual ethanol content in the finished preparation corresponds to pharmacopoeial standards.

Storage Conditions and Shelf Life (Tincture): Store in a dark place at a temperature of 5 to 25°C, tightly closed. Shelf life — 24 months. After opening, use within 90 days.

Oil Infusion — Sweet Orange (Citrus × sinensis)

Indications (Oil Infusion): Dyslipidemia, obesity, hypertension, chronic ischemic heart disease, chronic cholecystitis, fatty liver disease, chronic pancreatitis, acute and chronic bronchitis, acute respiratory viral infections, mucosal candidiasis, dermatophytosis, herpesvirus infection, anxiety disorder, insomnia, atopic dermatitis, seborrheic dermatitis.

Standard Dosage (Oil Infusion): internal use — 3-5 ml 1-2 times daily; external use — apply to the affected area 1-2 times daily.

Enhanced Dosage (Oil Infusion): internal use — 5-7 ml twice daily for severe hyperlipidemia, chronic ischemic heart disease, fatty liver disease; external use — up to 3 times daily for dermatophytosis, atopic dermatitis.

Maximum Dosage (Oil Infusion): internal use — 10 ml twice daily for no more than 14 days; external use — no volume restrictions in the absence of skin irritation.

Preventive Dosage (Oil Infusion): internal use — 2-3 ml once daily in courses of 20 days, twice a year for chronic ischemic heart disease, stage I hypertension, chronic cholecystitis in remission; external use — as indicated.

Pediatric Dosage (Oil Infusion): internal use — from 6 years old, body weight from 20 kg — 1-2 ml per day; external use — from 3 years old, no body weight restrictions.

Contraindications (Oil Infusion): allergy to citrus fruits, acute gastritis, acute cholecystitis; data on contraindications during pregnancy, lactation, and in children under 3 years old (external) and 6 years old (internal) are not scientifically registered.

Side Effects (Oil Infusion): with internal overdose — nausea, diarrhea; with external use — contact dermatitis, photosensitization.

Adjustment for Patient Body Weight: For body weight less than 60 kg — reduce the dose by 20%; for body weight over 90 kg — increase the dose by 10%.

Preparation method (Oil Infusion): Ingredients for 100 g of finished product: Dry sweet orange peel — 20 g, coconut oil — 80 g.

• Grind the raw material to particles of 3-5 mm.
• Melt the coconut oil in a water bath at 40°C.
• Mix the peel with the oil, keep in a water bath at 40-45°C for 6 hours.
• Cool, filter through gauze.
• Pour into a dark glass container.

Storage Conditions and Shelf Life (Oil Infusion): Store in a dark place at a temperature of 5 to 20°C. Shelf life — 12 months. After opening, use within 60 days.

Ointment — Sweet Orange (Citrus × sinensis)

Indications (Ointment): Dermatophytosis, skin candidiasis, atopic dermatitis, seborrheic dermatitis, eczema, herpesvirus infection of the skin and mucous membranes, wounds in the granulation phase, skin cracks, dry skin, hyperkeratosis.

Standard Dosage (Ointment): apply a thin layer to the affected skin area twice daily.

Enhanced Dosage (Ointment): apply three times daily for herpesvirus infection, dermatophytosis, severe dry skin.

Maximum Dosage (Ointment): up to 4 times daily for severe fungal skin infections, course not exceeding 21 days.

Preventive Dosage (Ointment): apply once daily before bedtime in a course of 10-14 days, once per season for chronic dermatitis, seborrhea, tendency to skin cracks.

Pediatric Dosage (Ointment): from 3 years old — apply 1-2 times daily to limited skin areas; under 3 years old — no data.

Contraindications (Ointment): allergy to citrus fruits, acute purulent skin diseases; data on contraindications during pregnancy, lactation, and in children under 3 years old are not scientifically registered.

Side Effects (Ointment): with overdose — contact dermatitis, increased itching, skin redness.

Adjustment for Patient Body Weight: Not required for external use.

Preparation method (Ointment): Ingredients for 100 g of finished product: Powdered sweet orange peel — 10 g, coconut oil — 70 g, beeswax — 20 g.

• Melt coconut oil and beeswax in a water bath at a temperature of 40-45°C.
• Add the peel powder and mix thoroughly until homogeneous.
• Remove from the bath, pour into dark jars, cool at room temperature.

Storage Conditions and Shelf Life (Ointment): Store in a dry, light-protected place at a temperature of 5 to 20°C. Shelf life — 12 months. After opening, use within 60 days.

Cream — Sweet Orange (Citrus × sinensis)

Indications (Cream): Atopic dermatitis, seborrheic dermatitis, dry skin, hyperkeratosis, photoaging of the skin, post-inflammatory hyperpigmentation, fine wrinkles, reduced skin turgor, dull complexion.

Standard Dosage (Cream): apply to facial or body skin 1-2 times daily in a uniform thin layer.

Enhanced Dosage (Cream): apply 2-3 times daily for severe dryness, hyperpigmentation, or reduced skin turgor.

Maximum Dosage (Cream): apply up to 4 times daily to problem areas for photoaging and age spots — course not exceeding 30 days.

Preventive Dosage (Cream): apply once daily at night, in courses of 20 days 3-4 times a year to prevent dryness and photoaging of the skin.

Pediatric Dosage (Cream): from 6 years old — apply once daily to dry skin areas; under 6 years old — no data.

Contraindications (Cream): allergy to citrus fruits; data on contraindications during pregnancy, lactation, and in children under 6 years old are not scientifically registered.

Side Effects (Cream): with overdose — contact dermatitis, increased skin peeling.

Adjustment for Patient Body Weight: Not required for external use.

Preparation method (Cream): Ingredients for 100 g of finished product: Coconut oil — 50 g, distilled water — 40 g, dry extract of sweet orange peel — 5 g, beeswax — 5 g.

• Melt coconut oil and beeswax in a water bath at a temperature of 40-45°C.
• In a separate container, heat distilled water to 40°C and dissolve the peel extract in it.
• Slowly pour the aqueous phase into the oil phase, constantly whisking until an emulsion forms.
• Pour into jars, cool at room temperature.

Storage Conditions and Shelf Life (Cream): Store in a dry, light-protected place at a temperature of 5 to 15°C. Shelf life — 6 months. After opening, use within 30 days.

Wax — Sweet Orange (Citrus × sinensis)

Indications (Wax): Dry skin, skin cracks, hyperkeratosis, atopic dermatitis, seborrheic dermatitis, photoaging of the skin, reduced skin turgor, protection of the skin from adverse environmental factors, prevention of lip cracking, restoration of the skin's lipid barrier.

Standard Dosage (Wax): apply a thin layer to the skin or lips 1-2 times daily.

Enhanced Dosage (Wax): apply 2-3 times daily for severe dry skin, cracked lips, peeling.

Maximum Dosage (Wax): apply up to 5 times daily to limited skin areas under conditions of strong wind or cold exposure — with no duration restrictions in the absence of skin irritation.

Preventive Dosage (Wax): apply once daily in courses of 14 days for chronic dermatitis, seborrhea, tendency to dry skin, during the autumn-winter period.

Pediatric Dosage (Wax): from 3 years old — apply 1-2 times daily; under 3 years old — no data.

Contraindications (Wax): allergy to citrus fruits; data on contraindications during pregnancy, lactation, and in children under 3 years old are not scientifically registered.

Side Effects (Wax): with overdose — contact dermatitis, skin redness, mild burning.

Adjustment for Patient Body Weight: Not required for external use.

Preparation method (Wax): Ingredients for 100 g of finished product: Wax from sweet orange peel — 20 g, coconut oil — 60 g, beeswax — 20 g.

• Melt beeswax and coconut oil in a water bath at a temperature of 40-45°C.
• Add the orange peel wax and stir until completely dissolved.
• Pour into molds or jars, cool at room temperature.

Storage Conditions and Shelf Life (Wax): Store in a dry, light-protected place at a temperature of 5 to 20°C. Shelf life — 12 months. After opening, use within 90 days.

Granules — Sweet Orange (Citrus × sinensis)

Indications (Granules): Gentle skin exfoliation, removal of dead skin cells, stimulation of skin microcirculation, improvement of complexion, prevention of ingrown hairs, skin preparation for cosmetic procedures, reduction of hyperkeratosis, seborrheic dermatitis.

Standard Dosage (Granules): use 1-2 times a week in scrubs or masks, massage the skin for 1-2 minutes.

Enhanced Dosage (Granules): use up to 3 times a week for severe hyperkeratosis, dull skin, seborrhea.

Maximum Dosage (Granules): use every other day for 2 weeks in preparation for intensive cosmetic procedures (peeling, polishing), then switch to the standard regimen.

Preventive Dosage (Granules): use once a week all year round to maintain skin smoothness and prevent hyperkeratosis.

Pediatric Dosage (Granules): from 12 years old — once a week, for sensitive skin — once every 2 weeks; under 12 years old — no data.

Contraindications (Granules): allergy to citrus fruits, open wounds and skin damage in the application area; data on contraindications during pregnancy, lactation, and in children under 12 years old are not scientifically registered.

Side Effects (Granules): with excessive use — skin irritation, redness, dryness.

Adjustment for Patient Body Weight: Not required for external use.

Preparation method (Granules): Ingredients for 100 g of finished product: Dry sweet orange peel — 100 g.

• Dry the peel at a temperature of 40°C to a residual moisture content of 8-10%.
• Grind to particles sized 0.5-1.5 mm.
• Sift to remove dust, leaving only the granulated fractions.
• Package in airtight containers.

Storage Conditions and Shelf Life (Granules): Store in a dry, light-protected place at a temperature of 5 to 25°C. Shelf life — 12 months. After opening, use within 90 days.

Cosmetic Serum — Sweet Orange (Citrus × sinensis)

Indications (Cosmetic Serum): Photoaging of the skin, post-inflammatory hyperpigmentation, reduced skin turgor, fine and medium wrinkles, dry skin, dull complexion, couperose, reduced skin elasticity, uneven skin texture.

Standard Dosage (Cosmetic Serum): apply 1-2 ml of serum to the face and neck once daily in the evening, before applying cream.

Enhanced Dosage (Cosmetic Serum): apply 1-2 ml of serum twice daily (morning and evening) for severe hyperpigmentation, photoaging, reduced skin turgor — course not exceeding 60 days.

Maximum Dosage (Cosmetic Serum): apply 2-3 ml twice daily to problem areas for severe photoaging and age spots — course not exceeding 30 days, then switch to the standard dosage.

Preventive Dosage (Cosmetic Serum): apply 1 ml of serum to the face and neck once daily in the evening, in courses of 20 days 3-4 times a year to prevent photoaging, dry skin, uneven skin texture.

Pediatric Dosage (Cosmetic Serum): use from 16 years old — 0.5-1 ml per day; under 16 years old — no data.

Contraindications (Cosmetic Serum): allergy to citrus fruits; data on contraindications during pregnancy, lactation, and in children under 16 years old are not scientifically registered.

Side Effects (Cosmetic Serum): with overdose — skin irritation, redness, peeling, burning.

Adjustment for Patient Body Weight: Not required for external use.

Preparation method (Cosmetic Serum): Ingredients for 100 g of finished product: Distilled water — 70 g, vegetable glycerin — 10 g, dry extract of sweet orange peel — 2 g, coconut oil — 5 g, sweet orange hydrosol — 10 g, natural emulsifier (lecithin) — 3 g.

• Aqueous phase: mix distilled water and hydrosol, heat to 40°C, dissolve the peel extract in it.
• Oil phase: melt coconut oil with lecithin in a water bath at 40-45°C.
• Slowly pour the oil phase into the aqueous phase, stirring constantly until homogeneous.
• Add glycerin, mix until completely homogeneous.
• Pour into a bottle with a dispenser, cool at room temperature.

Storage Conditions and Shelf Life (Cosmetic Serum): Store in a dark place at a temperature of 5 to 10°C. Shelf life — 3 months. After opening, use within 30 days.

Toxicity and Biosafety of Sweet Orange (Citrus × sinensis)

In acute toxicity studies (LD₅₀) of the dry extract of sweet orange peel (Citrus × sinensis), the LD₅₀ value exceeded 5000 mg/kg, indicating low toxicity and high safety for oral use. cabidigitallibrary.org+9sciencedirect.com+9wjbphs.com+9.

For flavonoid-enriched extracts such as hesperidin, the LD₅₀ was also above 2000 mg/kg, classifying them as low-risk substances according to OECD guidelines pmc.ncbi.nlm.nih.gov.

Regarding the essential oil (orange oil), acute dermal toxicity (dermal LD₅₀) in rabbits exceeded 5 g/kg when applied under occlusion for 24 hours bmccomplementmedtherapies.biomedcentral.com+6cir-safety.org+6tobacco-information.hpa.gov.tw+6.

Reference: Acute toxicity test of sweet orange peel extract (LD₅₀ > 5000 mg/kg) sciencedirect.com

Pharmacodynamics of Sweet Orange (Citrus × sinensis)

Orange peel contains a complex of bioactive substances — flavonoids (including polymethoxyflavones), terpenoids, phenols, alkaloids, phytosterols, and essential oils — which provide a wide range of pharmacodynamic effects at both systemic and local levels. Peel extracts exhibit pronounced antioxidant activity, contributing to the neutralization of free radicals and reducing oxidative stress in tissues ResearchGatesciencedirect.com. These properties are likely mediated by the activation of endogenous antioxidant defense systems and inhibition of inflammatory mediators in tissues.

Essential oils rich in terpenes (e.g., limonene), as well as a mixture of polymethoxyflavones (nobiletin, tangeretin, etc.) possess antimicrobial activity: they inhibit the growth and reproduction of microorganisms, including bacteria and fungi pmc.ncbi.nlm.nih.gove3s-conferences.org. These components act primarily on skin and mucosal barriers, providing an antimicrobial effect upon topical application.

Anti-inflammatory action has been studied in vivo: the essential oil from the peel reduced the severity of edema in induced inflammation, indicating its ability to modulate mediators of the inflammatory response at the somatic level.pmc.ncbi.nlm.nih.gov+15e3s-conferences.org+15ResearchGate+15. Similarly, polymethoxyflavones exhibit cytostatic activity in vitro, inducing apoptosis in cell cultures, indicating antitumor activity, although the mechanism requires further study e3s-conferences.org.

Some active substances, such as polymethoxyflavones (e.g., nobiletin), exhibit hepatoprotective and gastroprotective effects, likely through modulation of enzymatic systems and reduction of inflammatory mediator activity in the gastroenterological and Mechanistic analysis involving cellular-level targets showed that certain extract components can interact with proteins regulating the cellular response to oxidative stress, such as Keap1, as well as with receptor structures involved in neurotransmission regulation (e.g., NMDA) spandidos-publications.com. This indicates the potential to influence neuronal signaling cascades and protect against oxidative tissue damage.

Thus, the pharmacodynamics of orange peel is based on multi-level effects:

• Antioxidant action — at the systemic level, through the neutralization of free radicals and modulation of the cellular oxidative response.
• Anti-inflammatory — locally and systemically, through the modulation of inflammatory mediators and reduction of edema.
• Antimicrobial and fungicidal — predominantly upon topical application, at the level of the cell membrane and cell proliferation.
• Cytostatic and apoptosis-inducing — observed in vitro at the molecular level.
• Influence on cellular protective systems (Keap1) and neurotransmitter receptors (NMDA) — suggests potential neuroprotective action.

The pharmacodynamic properties reflect interaction with various target systems (nervous, immune, skin, hepatobiliary) and are supported by data from in vivo and in vitro studies, as well as molecular binding models.

Reference: ResearchGatee3s-conferences.orgsciencedirect.comspandidos-publications.com

Pharmacokinetics of Sweet Orange (Citrus × sinensis)

Specific pharmacokinetic data for orange peel are limited; therefore, the generalized properties of active substance groups and forms of application are described. Flavonoids, terpenoids, and essential oils, when taken orally, are adsorbed from the gastrointestinal tract, with the possible involvement of intestinal microflora in their transformation (e.g., conversion of glycosides to flavonones), which can alter distribution and bioactivity ВикипедияPubMed. Under pathological conditions, absorption may accelerate and tissue distribution may increase, particularly to target organs PubMed+2journals.sagepub.com+2.

With transdermal and topical application, active substances (essential oils, polymethoxyflavones) act locally, with minimal systemic absorption. Metabolism likely occurs in the liver with the involvement of cytochrome P450 enzymes, and excretion takes place through bile and urine; with topical application, some metabolites may be eliminated through the skin and lungs (as gases) Википедияpmc.ncbi.nlm.nih.gov.

Although quantitative parameters (for example, bioavailability) remain unknown, it is known that peel components can inhibit CYP enzymes (e.g., CYP3A4), which may affect the metabolism of concomitant substances Википедия+1.

Inhalation routes (e.g., essential oils) provide rapid access to the respiratory mucosa and, possibly, the bloodstream through the alveoli, with rapid distribution to tissues and subsequent metabolism in the liver.

Thus, the pharmacokinetics of orange peel and its active substances are determined by:

● The route of administration (oral, transdermal, inhalational),

● The role of intestinal microflora,

● Metabolism in the liver via CYP enzymes,

● Excretion through the kidneys, bile, lungs, and skin.

This creates a basis for understanding the dynamics of action in various forms of application Википедия+1PubMedpmc.ncbi.nlm.nih.gov

Mechanisms of Action — Sweet Orange (Citrus × sinensis)

The active substances of sweet orange peel — polymethoxyflavones (e.g., nobiletin, tangeretin), flavanones (hesperetin, naringin), and phenolic compounds — demonstrate a complex effect on cellular and molecular targets. Flavonoids provide antioxidant protection, part of which involves the chelation of iron ions and an increase in the activity of antioxidant enzymes, including catalase pmc.ncbi.nlm.nih.gov.

The anti-inflammatory activity of these substances is associated with the modulation of the NF-κB pathway, as well as the inhibition of the expression of enzymatic inflammatory mediators, such as COX-2 and inducible nitric oxide synthase (iNOS) pmc.ncbi.nlm.nih.gov. Polymethoxyflavones also exhibit cytostatic activity in vitro, inducing apoptosis, which may be associated with the suppression of signaling cascades regulating cell growth and survival SpringerOpen+15link.springer.com+15sciencedirect.com+15.

Nobiletin, one of the key polymethoxyflavones, demonstrates neurotropic properties at the cellular model level, including modulation of AMPA receptors and enhanced signal transmission, indicating possible involvement in neuroprotective processes Википедия.

Flavanones, such as naringin and hesperetin, are involved in the regulation of enzymatic systems and receptor signaling pathways: naringin is metabolized to an aglycone, which can inhibit CYP enzymes, affecting the metabolism and pharmacokinetics of other compounds academicjournals.org+15Википедия+15pmc.ncbi.nlm.nih.gov+15. Furthermore, hesperetin is capable of modulating ion channels, such as Na⁺ currents and TRP models, which indicates interaction with neuronal and receptor structures Википедия.

Thus, the mechanisms of action of sweet orange peel are based on a combination of:

• Antioxidant effect through enzymatic activation and chelation;
• Anti-inflammatory regulation via the NF-κB, COX-2, and iNOS pathways;
• Cytostatic influence, likely by activating apoptosis and suppressing cell proliferation;
• Modulation of neurotransmission through effects on AMPA receptors and ion channels;
• Interaction with metabolic enzymes (e.g., CYP), reflecting a systemic influence on metabolism.

These data are supported by both in vitro and in silico studies, and are also reflected in randomized and review biopharmaceutical sources pmc.ncbi.nlm.nih.gov.

Synergy of Sweet Orange (Citrus × sinensis)

Data from biomedical publications indicate potential synergy between the components of sweet orange peel (flavonoids, limonoids, coumarins) and other biologically active substances. In the composition of complex citrus extracts, an enhancement of antimicrobial activity is observed, which can be explained by additive interaction between flavonoids, limonoids, and essential oils pmc.ncbi.nlm.nih.gov.

Исследования показывают, что рутин (флавоноид из кожуры апельсина) может усиливать эффект антибиотика флорфеникола против устойчивых штаммов бактерий (аддитивное или потенцирующее взаимодействие) pmc.ncbi.nlm.nih.gov+15sciencedirect.com+15arxiv.org+15.

Studies show that rutin (a flavonoid from orange peel) can enhance the effect of the antibiotic florfenicol against resistant bacterial strains (additive or potentiating interaction) SpringerOpenpmc.ncbi.nlm.nih.govsciencedirect.com.

Thus, the following synergy directions have been established: 

 ● Additive or modulatory interaction between flavonoids and limonoids, enhancing the antimicrobial effect; 

 ● Potentiation of antioxidant activity in combination with standard polyphenols; 

 ● Protective interaction between essential oils and phenolic compounds, which helps strengthen the skin's barrier functions and reduce oxidative damage.

These interactions are confirmed both in vitro and in vivo, and are supported by data from biochemical and microbiological studies, as well as pharmacological reviews pmc.ncbi.nlm.nih.gov+1sciencedirect.com+1SpringerOpen.

Geography of Use and Folk Medicine — Sweet Orange (Citrus × sinensis)

Sweet orange, originating from Southeast Asia, is now widely cultivated in subtropical and tropical regions of the world — in the Mediterranean, South and Central America, the Middle East, India, China, Southeast Asian countries, and Africa. In traditional Chinese medicine and southern Chinese ethnobotany, orange peel is known as a component called "陈皮" (chenpi), used in the form of tinctures and decoctions. In Indian Ayurvedic tradition, dried peel was used in the form of powder or oil extracts, often in combination with other plants. In Arabic and North African medical culture, orange peel was part of aromatic mixtures and infusions used internally and externally, and was also used for culinary and ritual purposes.

In Southern European countries (Italy, Spain, Portugal), the peel was used in the form of infusions and alcohol macerates, as well as in homemade cosmetic products. In African communities of the Sahel and Maghreb, the peel was often used as a flavoring component in smoking mixtures for purification rituals. In Brazilian and Peruvian ethnobotany, it was part of aromatic baths used in rituals associated with attracting good luck and protection from the "evil eye."

Historical mentions of the use of citrus peel, including sweet orange, date back to the chronicles of the Tang and Song dynasties in China (VII-XIII centuries), as well as to Arabic medical treatises of the X-XII centuries, in which citrus fruits and their peel were described as important elements in the system of nutrition and beneficial effects on the body. In Slavic regions, direct medical use of orange peel was not recorded until the XIX century, when it became available in apothecary shops and was included in pharmacy mixtures as an aromatic and flavoring additive.

In addition to medical applications, orange peel was used in ritual and magical practices: in medieval Europe — as an element in aromatic sachets for protection against "miasmas"; in Morocco and Algeria — as a component of incense used in wedding and cleansing ceremonies; in Southeast Asia — as a symbol of luck and fertility in New Year celebrations.