Plantago major has been used widely since ancient times, to manage a wide range of diseases including constipation, coughs, and wounds. The aim of this study is to review the traditional application, botanical characterization, pharmacological activities, phytochemistry effects and toxicity of Plantago major. Moreover, electronic databases including Scopus, Medline, and Web of science were explored for this purpose. Plantago major has been prescribed in various forms such as roasted seeds, decoction, syrup, liniment, gargle, rectal enema, vaginal suppository, eye and nasal drop for each illness by TPM scholars. Some of its traditional properties including wound healing, antipyretic, antitussive, anti-infective, anti-hemorrhagic, anti-inflammatory, diuretic, laxative, astringent and hemostatic have been confirmed in recent researches. Its leaves and seeds have been used in almost all parts of the world for centuries as a wound healer, analgesic, antioxidant, and antibiotic, as well as an immune system modulator, antiviral, antifungal, and anti-inflammatory agent. Phytochemical investigations showed that the Plantago major contains volatile compounds, triterpenoids, phenolic acids, and flavonoids. Modern pharmacological studies have proven some of the traditional applications of Plantago major. Nevertheless, more investigations are required on this plant, because it has the potential to be used to produce various natural medications.
Uses/ Indications of Plantago
- Immune Enhancing Activity – Methanol extracts of P. major leaves, increase the creation of nitric oxide (NO), tumor necrosis factor-alpha (TNF-α) and stimulate lymphocyte proliferation, so activated macrophages are produced in a variety of cytotoxicity such as nitric oxide, TNF-α and lymphokines. As a result, it can prevent the development of tumors and infections . Plantago major shows immunomodulatory activity, increasing lymphocyte proliferation and secretion of interferon-γ at low concentrations (< 50 μg/ml), but at high concentrations, it can inhibit this property (< 50 μg/ml). The hot water extracts of Plantago major can help to improve leukemia, carcinoma and viral infections .
- Hepatoprotective Activity – In recent years, hepatic disorders have been the main cause of deaths around the world . In one model of animal study, extract of Plantago major seed exhibits the hepatoprotective activity by which the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) showed the reduction .
- Cure Gastrointestinal Problem – Due to the anti-inflammatory effect of Plantago major, it can be used to treat endoparasites and stomach problems in animals. The polyholozidic fraction separated from the leaves and seeds of some Plantago species (Plantago major, media, lanceolata) explains its gastroprotective action, and a laxative effect was obtained with higher doses of Plantago major . The seeds of the plant have a high gastroprotective effect in comparison to the leaves, which may be as a result of high content from mucilage. A water immersion-stress ulcer model was used on rats to test the plant extract’s ability to inhibit ulcers. Acidity and gastric fluid were significantly decreased by an extract which may be due to inhibition of gastric acid secretion and an increase of mucosal defensive factors . On the other hand, Plantago leaves extract decreased the motility of duodenum and also had antidiarrheal effect in oral administration . Plantago major seeds are recommended for inflammatory bowel disease (IBD). Although the oral administration of leaf extract can decrease gastric ulcers, the seed extract has no effect. But both seed and leaf extracts can decrease total acidity as well 
- Cure Pulmonary Disease – Plantago major inhibits mast-cell degranulation and can be used for treating asthma and allergic disease . It protects against pneumococcal infection in mice and the treatment of chronic bronchitis 
- Anti-inflammatory Agent for Urinary Tract – Plantago major has diuretic effects  and can also inhibit the activity of angiotensin converting enzyme . Another study on an extract of Plantago major showed that it is more efficient than allopurinol and potassium citrate in inhibiting the size of the calcium oxalate crystal in-vitro and it can be consumed to improve urolithiasis .
- Dermatologic effects – Plantago major is an effective herb in the management of acute urticaria . Ursolic acid, oleanolic acid, and α-linolenic acid are three Plantago major components that have shown inhibitory effects on COX-2 catalyzed prostaglandin production. Luteolin (one of the flavonoids) also has the ability to suppress leukocyte migration and inhibit mast cell degranulation which all together can be considered as anti urticaria treatment strategies .
- Anti-hypercholesteremia, Anti-atherosclerosis and Hypoglycemic effect – Plantago major leaves can inhibit progressions of atherosclerosis and hypercholesteremia in animals via the lecithin/cholesterol ratio . Plantago major seeds have a hypoglycemic effect in mice (43). Plantagoside and its aglycone in Plantago major seeds inhibit protein cross-linking glycation and have potential beneficial applications in the prevention of diabetic complications .
- Antinociceptive Effects – Methanolic extracts of leaves, seeds or aqueous extract of the plant have shown anti-inflammatory and analgesic activities through inhibition of prostaglandins synthesis .
- Antioxidant and Free Radical Scavenging Activity – Ethanolic hot and cold water extracts of Plantago major leaves and seeds have antioxidant activity . Plantago major contains flavonoids such as luteolin, apigenin, hispidulin and baicalein, which can induce carcinoma cell death. In addition, Plantago extracts have inhibitory and cytotoxic effects on breast adenocarcinoma and melanoma cell lines and these preliminary results could be justified by the cytotoxic activity of the flavone, luteolin-7-O-β-glucoside, the major flavonoid in Plantago species .
- Anti-infective, Antibiotic, Antifungal, Antiviral, Antimalarial and Anti-giardiasis Activity – Some types of Plantago major extract were effective in the treatment of fungal, bacterial and viral infections. Anti-malarial and anti-Giardia effects of the plant have been proven as well . However, the aqueous extract of Plantago major had a slight anti-herpes virus activity versus the caffeic acid, which exhibited the strongest activity against HSV-1, HSV-, and ADV-3. However, chlorogenic acid possessed the strongest anti-ADV-11 activity . Ethyl alcohol extract showed antibacterial activity against E. coli and Bacillus cereus and acetone extract were effective on bacteria species (Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Proteus mirabilis, Salmonella enteritidis) in different concentrations . Plantago major extract also showed acceptable potency against C. albicans (ATCC 66027) comparable to synthetic antifungal agents .
- Anticancer and Cytotoxic Activity – Methanolic Plantago major extract was evaluated for cytotoxic activity against three human cancer cell lines including the human renal adenocarcinoma (TK-10), the human breast adenocarcinoma (MCF-7) and the human melanoma (UACC-62). Flavonoids, flavone and luteolin are the main factors in cytotoxic activity . Plantago major may be partially effective in preventing carcinogenesis . The cytotoxic activity of Plantago major methanol extract on human transformed cells: HCT-15 (colon carcinoma), SQC-UISO (cervical carcinoma), OVCAR (ovary carcinoma) and KB (nasopharynx carcinoma) has also been evaluated, in vitro . Aqueous and methanol extracts of Plantago major also stimulate cell proliferation in bone marrow and spleen cell cultures. Although the same number of cells was cultured in both types of tumor, cell population was significantly higher in spleen cultures than in bone marrow cultures. In fact, oleanolic acid and ursolic acid stimulated the proliferation of splenocytes and enhanced the recovery of the hematopoietic system .
- Wound Healing Effects – Plantago major was used in wound healing and the leaves were used as a remedy of wounds. Anti-inflammatory action is via a complex event linked to tissue damage whether by bacteria, physical trauma, chemical, heat or any other phenomenon. Also, the inflammatory response is the critical protective reaction to these kinds of injures remarked by redness, fever, edema (swelling) and pain in involved tissue (32). In an animal study, water extract of Plantago major is recommended as a suitable substitute for silver sulfadiazine, especially when applied in 50% concentration in wound burn healing . Polyphenols especially plantamajoside are considered as the main significant compounds for wound healing .
Dosage of Plantago
- Dosage: 15-20 drops three times daily orally in some water. Not recommended whilst pregnant or breastfeeding.