Phytochemistry and Pharmacology of Mesua ferrea Linn. – A Review

Nishendu P. Nadpara¹*, Jagruti P. Vaghela¹, Parula B. Patel¹

¹Department of Quality Assurance, S. J. Thakkar Pharmacy College, Rajkot, Gujarat, India

ABSTRACT:

Many plants have not been investigated thoroughly which are used traditionally as a medicine to cure the diseases and are found commonly. Medicinal plants can play vital role in the development of new drugs. It is necessary to conduct the study of these plants. Mesua ferrea Linn. (Family- Guttiferae), commonly known as ‘Nagchampa’, is one such plant which has many potential therapeutic uses in diseases like rheumatism, asthma, inflammation, fever, dyspepsia, renal diseases, dysentery, bleeding piles and in bacterial and fungal infections. It contains very important class of compounds like coumarins, xanthones, pyranoxanthones, flavonoids, a few terpenoids and steroids. They are easily isolated from the plant and can act as precursors of many therapeutically important compounds. The present review is based on an extensive literature search of reputed books, websites and journals. It gives the idea about the research done on this plant so far and the work that can be done in the future.

KEYWORDS: Coumarins, Guttiferae, Mesua ferrea, Nagchampa, Xanthones.

INTRODUCTION:

Mesua ferrea Linn. (Family- Guttiferae), commonly known as ‘Nagchampa’, is a common ayurvedic herb. It contains very important class of compounds like coumarins, xanthones, pyranoxanthones, flavonoids, a few terpenoids and steroids which are very important phytoconstituents. Mesua ferrea has been reported to give very important pharmacological activities. They are easily isolated from the plant and can act as precursors of many therapeutically important compounds. The present review is based on an extensive literature search of reputed books, websites, journals and remarks on the study done up to now and the work that can be done in the future.

Vernacular Names ^{1, 2}

Sanskrit : Kesara, Nagapuspa, Naga, Hema, Gajakesara

Hindi : Nagkesara, Pila Nagesara

Bengali : Nsgesvara, Nagesar

English : Cobras Saffron

Gujarati : Nagchampa, Nagkesara, Sachunagkeshara, Pilunagkesar, Tamranagkesar

Marathi : Nagkesara

Telugu : Nagachampakamu, Kesaramu

Tamil : Nangu, Naugaliral, Nagachampakam

Kannad : Nagakesari, Nagsampige

Assam : Nageshvar, Nahar

Andamans : Gangane

Malyalam : Nangaa, Nauga, Peri, Nagppu, Nagappovu, Veluthapala

Orissa and Punjabi : Nageswar

Urdu : Narmushk, Nagkesar

Geographical Source³

Mesua ferrea commonly found in the Himalayas from Nepal eastwards, in north eastern India, Deccan Peninsula and the Andaman Islands, ascending to an altitude of 1,500 m. In India, it is mainly found in Tamilnadu, Kerala, Assam, Eastern Ghats, Western Ghats and Andaman Islands.

Taxonomic Classification⁴

Kingdom : Plantae

Division : Magnoliophyta

Class : Magnoliopsida

Order : Malpighiales

Family : Clusiaceae

Subfamily : Kielmeyeroideae

Tribe : Calophylleae

Genus : Mesua

Species : Mesua ferrea

Description²

Mesua ferrea Linn. (Family- Guttiferae) is a medium-sized to large evergreen tree with short trunk, often buttressed at the base. Bark is grayish or reddish brown and exfoliating in large thin flakes. Leaves are lanceolate, coriaceous and generally covered with a waxy bloom underneath. Leaves are red when young. Flowers are large, solitary or in clusters of 2-3, white and fragrant. Fruits are ovoid, nearly woody, 2.5 to 5 cm long, with persistant calyx. Seeds are 1 to 4 in number, dark brown and having diameter 2.5 cm. Seed kernels form 53-73 % of the weight of seeds. Cotyledons are fleshy and oily.

Figure 1: Mesua ferrea Linn.

Figure 2: Structures of Phytoconstitutes isolated from plant M. ferrea.

Figure 3: Structures of Phytoconstitutes isolated from plant M. ferrea.

Pharmacognostic Study¹

Macroscopic characters of stamen:

Stamen consists of anther, connective and filament, coppery or golden brown, filament united at base forming a fleshy ring, each stamen is 0.9-1.9 cm long, anther about 0.5 cm long, linear, basifixed, containing pollen grains, filament 0.8 to 1.0 cm long, slender, filiform, more or less twisted, soft to touch, quite brittle, connective not visible with naked eye, odour is fragrant and taste is astringent.

Microscopic characters of stamen:

Androecium:

Anther shows golden-brown, longitudinally dehiscent anther wall, consisting of thin walled, parenchymatous cells, pollen grains numerous in groups or in single, yellowish and thin walled, many pollen grains having 1-3 minute, distinct protuberances on walls, thick-walled, exine and intine distinct.

Powder:

Brown shows elongated cells of filament, connective and numerous golden yellow pollen grains having 1-3 protuberances.

Uses^{2,
3, 5}

The plant has a very wide medicinal use. Seed oil is used in rheumatism. It is used in bleeding piles, burning feet, dysentery, asthma, excessive perspiration, vomiting and cough. It is used to treat fever and dyspepsia. It is diuretic, so it can be used to treat renal disorder. It has anti-inflammatory, hypotensive, analgesic, antibacterial, antifungal and anthelmintic activity. Leaves are used in the form of poultice which is applied to head in severe colds. Bark and root in decoction or infusion or tincture is a better tonic and are useful in gastritis and bronchitis. Fixed oil express from the seeds is used as an application for cutaneous affections, such as sores, scabies and wounds. According to Unani system of medicine it was used as tonic for heart, expels winds, antispasmodic and emmenagogue. Leaves and flowers are used in scorpion-stings. Important formulations of the plant are SEPTILIN and STYPLON which are efficacious in treating chronic gingivitis. Another formulation is FEMIFORTE which is used to treat non-specific leucorrhoea.

Phytochemical Constitutes^5-10

Seed kernels yield 65% of oil. Fatty acid composition of the oil is: Myristic (0.1-1.8 %), Palmitic (4.9-26.9 %), Stearic (9.2-15.8 %), Arachidonic (0.8-2.7 %), Oleic (49.2-65.4 %), Linileic (3.2-21 %).

Oil cake or seed meal contains 28.7 % protein. Seed oil contains Coumarin – Mesuarin. Mammeisin, Mesuagin, Mammeigin, Mesuol, Mesuone are also isolated from seed oil (Figure 2). Phenolic constituents are also found. Leaves contain the Flavonone Glycosides – Mesuein. Stem-bark contains bis-xanthones - Mesuabixanthone A and B. Flowers contain volatile oil. Stamens Contain Mesuaferrone A and B, Mesuaferrol, Mesuanic acid, α and β amyrin and β– sitosterol (Figure 3).

New pigments isolated from heartwood are: Mesuaxanthone A and B and Euxanthone. Two new pyroxanthones- Mesuaferrin A and Mesuaferrin B (Figure 4) were isolated from the root bark of the plant. Their structures were also elucidated.

Pharmacological Activity

Analgesic activity

The n-hexane extract of M. ferrea produced significant antinociceptive action when administered orally, against chemical (acetic acid-induced visceral pain) models of nociception in mice. Acetic acid induced abdominal constriction is a sensitive method to evaluate the potential analgesic activity of drugs.

The nociceptive activity produced by acetic acid may be due to the release of cytokines such as TNF-α, interleukin-1β and interleukin-8, by resident peritoneal macrophages and mast cells. Anti-nociceptive action of n-hexane extract may be due to inhibition of the release of TNF-α, interleukin-1β and interleukin-8 by resident peritoneal cells¹¹

CNS activity

All the Xanthones of plant M.ferrea produced CNS depression in mice which is characterized by ptosis, sedation, decreased spontaneous motor activity and loss of muscle tone. The CNS depressant effect predominated at a dose level of 200 mg/kg. The depressant effect was observed within 15 min after the administration of the test compounds and the effect lasted for 60-90 min. Xanthones of M. ferrea were administered to groups of 5 mice each in doses of 10, 25, 50, 100, 200 and 500 mg/kg. Gross behavioral changes were recorded at 15, 30, 60 and 120 min after the administration of the test compounds and they were compared with the gum acacia treated controls¹².

Anti-inflammatory activity

Xanthones of M. ferrea produced anti-inflammatory activity in rats. It was tested by the carrageenin induced hind paw oedema, cotton pellet granuloma and granuloma pouch techniques. The anti-inflammatory effect of the xanthones was evaluated using albino rats. The xanthones were administered at a dose level of 50 mg/kg of body weight, while the positive control animals were administered phenylbutazone (100mg/kg) or dexamethasone (1mg/kg)¹². Mesuol exhibited significant reduction in carrageenan induced paw edema in a dose dependent manner. It may be due to inhibition of release of pro-inflammatory mediators of acute inflammation such as histamine and prostaglandin¹³.Crude extract of M. ferrea flowers found to exhibit significant anti-inflammatory activity. Extract produced significant reduction in paw edema, observed from the second hour at the 200mg/kg 400mg/kg dose level, but it was not observed from the second hour at the 100mg/kg dose level¹⁴.

Antibacterial activity

Methanolic extract of flowers of M. ferrea was found to produce activity against Staphylococcus aureus and Pseudomonas aeruginosa. Antibacterial activity was checked by measuring zone of inhibition by using sabouraud dextrose media for the growth of bacteria¹⁵. Mesuol and Mesuone which were found to present in seed oil, showed activity against Staphylococcus aureus and Mycobacterium phlei¹⁶. In vitro antibacterial activity of various plant parts were measured by the standard disc diffusion method. Petrolium ether, chloroform and ethanol extracts of various plant parts showed antibacterial activity. Nutrient agar medium was used to determine antibacterial activity. Petrolium ether extract of seeds showed activity against Bacillus subtilis, Bacillus megaterium, Staphylococcus aureus, Streptococcus β-haemolyticus, Shigella sonnei, Escherichia coli, Klebsiella species, Shigella boydii, Shigella flexneriae, Shigella dysenteriae, salmonella typhi and Pseudomonas aeruginosa. Chloroform extract of seeds showed activity against Bacillus subtilis, Bacillus megaterium, Staphylococcus aureus, Streptococcus β-haemolyticus, Escherichia coli, Klebsiella species, Shigella dysenteriae, salmonella typhi and Pseudomonas aeruginosa. Ethanolic extract of seeds showed activity against Bacillus megaterium, Staphylococcus aureus, Streptococcus β-haemolyticus, Shigella sonnei and Escherichia coli. Petrolium ether, chloroform and methanolic extracts of stem bark showed activity against Bacillus subtilis, Bacillus megaterium, Staphylococcus aureus, Streptococcus β-haemolyticus, Sarcina lutea, Shigella sonnei, Escherichia coli, Klebsiella species, Shigella shiga, Shigella boydii, Shigella flexneriae, Shigella dysenteriae, Salmonella typhi and Pseudomonas aeruginosa. Petrolium ether and chloroform extracts of leaves showed activity against Bacillus subtilis, Bacillus megaterium, Staphylococcus aureus, Streptococcus β-haemolyticus, Sarcina lutea, Shigella sonnei, Escherichia coli, Klebsiella species, Shigella shiga, Shigella boydii, Shigella flexneriae, Shigella dysenteriae, salmonella typhi and Pseudomonas aeruginosa. Ethanolic extract of leaves showed activity against Staphylococcus aureus, Streptococcus β-haemolyticus, Sarcina lutea, Shigella sonnei, Escherichia coli, Klebsiella species, Shigella shiga, Shigella flexneriae, Shigella dysenteriae and salmonella typhi¹⁷. 4-Alkyal, 4-Phenylcoumarins from the plant M. ferrea showed activity against multi-drug resistant gram-positive bacteria such as staphylococcus aureus and other strains¹⁸.

Antifungal activity

In vitro antifungal activity of various plant parts were measured by the standard disc diffusion method. Petrolium ether, chloroform and ethanol extracts of various plant parts showed antifungal activity. Potato dextrose agar medium was used to determine antifungal activity. Petrolium ether extract of seeds showed activity against Penecillum notatum, Asperagillus niger, Trichoderma viride and Candida albicans. Chloroform extract of seeds showed activity against Penecillum notatum, Asperagillus niger, Trichoderma viride and Hensinela californica. Ethanolic extract of seeds showed activity against Penecillum notatum, Asperagillus niger, Candida albicans and Hensinela californica. Petrolium ether, chloroform and Ethanolic extracts of stem bark showed activity against Penecillum notatum, Asperagillus niger, Trichoderma viride, Candida albicans and Hensinela californica. Petrolium ether extract of leaves showed activity against Penecillum notatum, Asperagillus niger, Trichoderma viride, Candida albicans and Hensinela californica. Chloroform and ethanolic extract of leaves showed activity against Penecillum notatum, Asperagillus niger, Trichoderma viride and Candida albicans¹⁷.

Antioxidant and Hepatoprotective activity

Methanolic extract of flowers of M. ferrea shows antioxidant and hepatoprotective activity in female wistar mice at the dose of 100 mg/kg of body weight. The values of all enzymatic oxidants such as catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase were decreased in the control infected rat in all organs. It may be due to the additive and synergistic antioxidant activity of phytochemicals present in the plant¹⁹.

Antimalarial activity

4-Alkyal, 4-Phenylcoumarins from the plant M. ferrea showed weak antiprotozoal activity. It showed activity against Plasmodium falciparum which is responsible for the lethal malaria¹⁸.

Antivenom activity

The aqueous extract of leaves of plant M. ferrea showed activity against Heterometrus laoticus scorpion venom. Chick embryonic fibroblast cells were used for screening plants species with activity against cell lysis after Heterometrus laoticus venom treatment. The plant showed good results in this study²⁰.

Anti-arthritic activity

The petroleum ether, methanol and ethyl acetate extracts of seeds of M. ferrea showed anti-arthritic activity. The anti-arthritic activity was evaluated by formaldehyde induced arthritic model and Complete Freund’s Adjuvant (CFA) induced arthritis in rats. Treatment with the plant extracts produces inhibition of paw edema and percentage inhibition of paw edema was taken as a response. The anti-arthritic activity of M. ferrea seeds may be due to the presence of active constituents like fixed oil and xanthones²¹.

Smoke repellency and Mosquito larvicidal activity

Chloroform: methanol (1:1 v/v) extract of M. ferrea can be used effectively in the mosquito control programmes. Smoke from M.ferrea can play an important role in to interrupt transmission of disease where mosquitoes act as vector at the individual level. Petroleum ether, chloroform: methanol (1:1 v/v) and ethyl acetate extracts of mature plant leaves were investigated to establish its biocontrol potentiality under laboratory condition against larvae of Cx. Quinquefasciatus at different concentrations²².

Physicochemical Evaluaton²³

Table 1: Physicochemical evaluation of plant M. ferrea.

Sr. No.	Parameters	Value
1	Loss on Drying (% w/w)	6.78
2	Ash value (% w/w)	4.84
3	Acid insoluble ash (% w/w)	2.15
4	Alcohol soluble extractive (% w/w)	19.48
5	Water soluble extractive (% w/w)	15.26

Important Formulations^{1, 5, 23}

Table 2: Important formulations of plant M. ferrea with uses.

Sr. No.	Formulation	Manufacturer	Use
1	Candanabalalaksadi Taila	--	Gout, Oedema, Disease of urinary bladder, Bleeding disorder.
2	Kumaryasava	Dabur Health Care
3	Nagkesaradi churna	--
4	Haridra Khanda	Nagarjuna	Urticaria
5	Septilin	Himalaya Drug Company	Upper and Lower respiratory tract infections, allergic disorders, skin and soft tissue infections.
6	Styplon	Himalaya Drug Company	Bleeding gums, Bleeding hemorrhoids, hematuria, abnormal uterine bleeding
7	Femiforte	Charak pharmaceuticals	Used to treat excessive vaginal discharge due to fungal / bacterial / protozoal infection.

CONCLUSION:

Mesua ferrea is a very important plant that contains fatty acids, proteins, coumarins, flavonoids, xanthones, bis-xanthones, sterols, some phenolic and volatile oil constituents. These phytoconstitutes give very good anti-bacterial anti-fungal, anti-inflammatory, antioxidant, hepatoprotective, anti-arthritic and anti-venom and CNS activity. It can be used in diseases like rheumatism, bleeding piles, dysentery, asthama, genitor-urinary diseases, wounds and skin diseases. This plant has been reported to possess good therapeutic action against many of such diseases. The present review can give a way for a thorough evaluation and documentation of this plant. Further research on this plant can prove to be very fruitful for mankind.

REFERENCE:

1. The Ayurvedic Pharmacopoeia of India, Ministry of Health and Family Welfare, Department of Indian System of Medicine and Homoeopathy, New Delhi, 1^st Edition, I (II); 1999: 118-119.

2. Anonymous, The Wealth of India, Raw Materials, Council of Scientific and Industrial Research, New Delhi, VI; 2005: 349-352.

3. Nadkarni KM, Indian Materia Medica, Bombay Popular, Mumbai. 2005; Volume I: 792-794.

4. Available from: URL: http://zipcodezoo.com/Plants/M/Mesua_ferrea/

5. Anonymous, The Wealth of India, First Supplement Series (Raw Materials), Council of Scientific and Industrial Research, New Delhi, IV; 2003: 128-129.

6. Rastogi RP, Mehrotra BN et al. Compendium of Indian Medicinal Plants, Central Drug Research Institute, Lucknow, I; 2004: 273.

7. Rastogi RP, Mehrotra BN et al. Compendium of Indian Medicinal Plants, Central Drug Research Institute, Lucknow, II; 2006: 456.

8. Rastogi RP, Mehrotra BN et al. Compendium of Indian Medicinal Plants, Central Drug Research Institute, Lucknow, IV; 2002: 472.

9. Rastogi RP, Mehrotra BN et al. Compendium of Indian Medicinal Plants, Central Drug Research Institute, Lucknow, V; 2005: 543.

10. Gwendoline Cheng Lian Ee et al. Pyranoxanthones from Mesua ferrea. Molecules. 16; 2011: 5647-5654.

11. Sheikh ZR et al. Analgesic Activity of Mesua ferrea Linn. The Dhaka University Journal of Pharmaceutical Sciences. 5(1-2); 2006: 73-75.

12. Gopalakrishnan C et al. Anti-inflammatory and CNS Depressant activities of xanthones from Calophyllum inophyllum and Mesua ferrea. Indian Journal of Pharmacology. 12(3); 1980: 181-191.

13. Chahar M et al. Anti-nociceptive and Anti-inflammatory activity of mesuol isolated from Mesua ferrea L. seed oil. International Journal of Current Pharmaceutical Research. 4(1); 2012: 51-54.

14. Tiwari P, Nandy S, Screening of anti-inflammatory activity of Mesua ferrea Linn. Flower. International Journal of Biomedical Research. 3(5); 2012: 245-252.

15. Panthi MP, Chaudhary RP, Antibacterial activity of some selected folklore Medicinal plants from West Nepal. The Scientific World Journal. 4(4); 2006: 16-21.

16. Chakraborty DP et al. On the antibiotic properties of some constitutes of Mesua ferrea Linn. 25B (1); 1958.

17. Sayeed MA et al. Anti-microbial screening of Cassia fistula and Mesua ferrea. Journal of Medical Science. 4(1); 2004: 24-29.

18. Verotta L et al. 4-Alkyl- and 4-phenylcoumarins from Mesua ferrea as promising multidrug resistant antibacterials. Phytochemistry. 65; 2004: 2867–2879

19. Mishra P et al. In vivo antioxidant activity and hepatoprotective effects of methanolic extract of Mesua ferrea linn. International Journal of Pharmatech Research. 1(4); 2009: 1692-1696.

20. Daduang S et al. Screening of plants acting against Heterometrus laoticus scorpion venom activity on fibroblast cell lysis. Journal of Ethnopharmacology. 130(2); 2006: 201-207.

21. Jalalpure SS et al. Antiarthritic activity of various extracts of Mesua ferrea Linn. Seed. Journal of Ethnopharmacology. 138(3); 2011: 700-704.

22. Chandra G et al. Smoke repellency and mosquito larvicidal potentiality of Mesua ferrea Linn. leaf extracts against filarial vector Culex quinquefasciatus Say. Asian Pacific Journal of Tropical Biomedicine. 2011: S119-S123.

23. Joseph CR et al. Pharmacognostical study of Nagakeshara (Mesua ferrea Linn.) - An Ingredient in Vyaghrihareetaki Avaleha. International Journal of Research in Ayurveda and Pharmacy. 1(2); 2010: 264-272.