Biological, chemical and pharmacological aspects of Madhuca longifolia

Dhruv Jha, Papiya Mitra Mazumder

Birla Institute of Technology, Mesra 835215, Ranchi, India

1. Introduction

From ayurvedic era, herbal medicines are considered as the backbone of traditional system of medicine, as they have potent pharmacological effect, and hence are considered to be potential source of new drug development[1]. More than 75% of the population in developing countries still depends on traditional medicines. It has been found from scientific intervention that plant derived compounds show broad spectrum of efficacy and safety with comparatively lesser side effect as compared to synthetic molecules.Thus there is a need to increase screening of plants having medicinal value[2,3].

Madhuca longifolia(M. longifolia) also termed as mahua or butter nut tree (Mahva, Mohva, Mohua, Erappe, Ippa, Iluppai, Madhukah,Irippa), belong to family sapotaceae[4]. These are medium evergreen deciduous tree, distributed widely across India, Nepal, and Sri Lanka. Various parts ofM. longifoliais used in traditional and folklore system of medicine, due to its various pharmacological properties[5,6]. Therefore it is also termed as universal panacea of ayurvedic medicine[7]. Different parts ofM. longifoliahas shown efficacy in thetreatment of epilepsy,diabetes, inflammation, bronchitis, ulcer and other diseases[8-10].Madhucaoil extracted from seed is used as biofuel, edible fats and has shown good antioxidant and antimicrobial properties[10-12]. The flowers are well known for its reducing sugar content and have been used as cooling agent, astringent, demulcent and clinical study proves its activity in increasing the sperm count[13,14]. Leaves ofM. longifoliaare used in Cushing’s disease and bronchitis and have antioxidant properties[14,15]. The barks have shown remedy for itching, swelling, snake poisoning and diabetes[16,17].

2. Botanical description

M. longifoliatrees are normally 15-16 m high, with clustered leaves at the end of branches. The barks are brownish to yellowish grey in colour. Elliptic flowers are small, cream coloured and are produced in clusters[16,17].

Its taxonomy and nomenclature are as follows: Plant name:M.longifolia; Kingdom: Plantae; Phylum; Tracheophyta; Order:Ericales; Family: Sapotaceae; Genus:Madhuca; Species:longifolia.

3. Traditional uses

In traditional and folklore medicine,Madhucaplays an immense role for the prevention and cure of many diseases. Different part shows versatile pharmacological activity. Flowers have been used for bronchitis, demulcent, diuretic, analgesic, as cooling agents and tonic. It is also used for treatment against helminths infestation as well as pharyngitis and also shows aphrodisiac activity. The bark also exhibits various pharmacological properties and is used for bronchitis, diabetes, rheumatism, bleeding, ulcer, tonsillitis,pharyngitis and spongy gums. It has also shown to be good remedy against swelling, snakebite poisoning, itching and fractures. Leaves ofMadhucahave been used for the treatment of diabetes, Cushing’s disease, bronchitis, rheumatism, haemorrhoids, cephalagia, intestinal diseases, and dermatopathy. The leaves are used as hepatoprotectants,for wound healing activity and as antioxidant. Seed fat has emulscent property, are used in hypoglycaemia, rheumatism, headache, in piles as a laxative, in skin disease and also as a galactogogue.Madhucaroots have shown its action against inflammation, and as antipyretic.The roots are also used in diarrhea, as antioxidant, and for the treatment of pthisis and scrofula[12,17,18].

4. Chemical constituents

The flowers mostly contain vitamin A and vitamin C[19,20].Many phytoconstituents have been found in bark, which may be responsible for various activities[21,22]. It constitutes of oleanic acids, α-spinasterol, α-amyrin acetate, erythrodiol monocaprylate betulinic acid, α-terpeniol, and sesquiterene alcohol[23,24]. Fruits ofMadhucachemically consists of quercetin, dihydroquecertin,β-sitosterol, as well as α and β amyrin acetates[25,26]. Main constituents ofM. longifoliaseeds are some amino acids like glycine,alanine, cysteine, leucine, and isoleucine. It also consists of arachidic,oleic, linoleic, myristic, palmitic and stearic acids[27-29]. Quercetin,Misaponin A and B are also found in seeds. Several bioactive constituents have been isolated and identified in the leaves ofMadhucalike sitosterol, quercetin, 3-O-Lrhamnoside, stigmasterol,n-hexacosanol,n-octacosanol, carotene, myricitin, erthrodiol, βDglucoside, β sitosterol, 3β caproxyolcan 12 en 28-ol, 3 galactoside,3-O-arabinoside, and xanthophylls[26].

5. Scientific proven uses of Madhuca species

Several scientist substantiated the traditional observation, through various experimental procedures. The bark and leaves are the frequently used parts. The ease of availability of leaves and bark helps in extensive use in traditional system of medicine. The presence of different phytoconstituents like alkaloids, terpenoids,saponins, and flavonoids is proposed to be responsible for various pharmacological actions. Scientific evaluations and study authenticates the ethnomedicinal and novel pharmacological effects.Different pharmacological findings obtained from various parts ofM. longifoliahave been tabulated in Table 1.

Table 1Pharmacological studies of various plant parts.

5.1. Antioxidant activity

Many scientific works prove that free radicals including active nitrogen species and reactive oxygen species are the primary cause in initiation of cellular damage resulting pathological changes and many diseases. Studies of Royet al. and Agrawalet al. had shown that the ethanolic extract of bark ofMadhucaexhibits significant antioxidant potential[27,28]. The extract also averts the lipid peroxidation. Palaniet al. studied thein-vitrofree radical scavenging capacity of leaves and subsequently thein-vivoantioxidant assessment was carried out by glutathione and lipid peroxidation method is done forin-vivoassessment[40].

5.2. Anti-inflammatory activity

Inflammation is a complex response of a body to the external stimuli. Formation of inflammatory leukcocytes in this process leads to the excess generation of free radicals which alters the cellular function and damages the organs by initiating and promoting the various diseases[46]. Several scientific studies on the ethanolic extract ofMadhucabark and seeds had proven anti-inflammatory activity. The crude ethanolic extract, saponin mixture and methanolic bark extract ofM. longifoliaextract has shown significant effect on inflammation induced by carrageenan as followed by the study of Agrawalet al. and Gaikwadet al. and there was size reduction in paw odema[34,43].

Similar research was carried out and has shown that the crude alkaloid extract ofMadhucaspecies also exhibits potent antiinflammatory activity. On the other hand, ethanolic extract and saponin mixture at dose of 10-15 mg/kg markedly reduces the rat paw oedema induced by formaldehyde, carrageenan and cotton pellet granuloma. However, a dose-dependent activity was found only on the carrageenan induced model[47]. The proposed mechanism of action was that constituents ofMadhucainhibit the prostaglandin synthesis as well as its mediators in synthesis. It may also act by reducing the intercellular cell adhesion molecule-1 expression which is induced by tumor necrosis factor α[47].

5.3. Analgesic activity

The drugs used to prevent algesia are termed to be analgesic.Studies suggest that analgesic activity ofMadhucais mediated by central or peripheral mechanism. Experimental works of Chandra have demonstrated the analgesic activity ofMadhuca[35]. Study of Chandra states that the alcoholic extract of flowers has good analgesic activity against hot plate and tail flick method showing central analgesic activity in dose-dependent manner[35]. The dose of 4-64 mg/kg showed a marked increase in analgesic efficacy on all nociceptive methods. The methanolic extract at dose of 50-200 mg/kg i.p markedly reduces acetic acid induced pain in a dosedependent manner showing that the extract possessed peripheral analgesic activity[47]. Madlongoside, an isolated compound obtained from theMadhucabark, showed a significant central analgesic activity when assessed by hot plate method.

5.4. Antipyretic activity

Elevation of body temperature from normal is termed as pyrexia.Madhucaalso exhibits febrifuge action. Methanolic extract of aerial part showed significant dose-dependent inhibition on temperature elevation when evaluated by Brewer’s yeast induced pyrexia model[47].

5.5. Anti-ulcer activity

Peptic ulcer is chronic inflammatory condition referring to the sores and ulcer in the lining of stomach and duodenum[29]. Experimental works of Kalaivani and Jegadeesan had shown that ethanolic extract of bark possess significant antiulcer action[36]. Study of Mohod and Bodhankar had proven the antiulcer activity of aqueous extract of leaves. The crude ethanolic extract of seeds ofMadhucashowed significant protective effect in pylorus ligation induced gastric ulcer model with a marked decrease in ulcer index as compared to vehicle[48]. This action may be due to its activity through prostaglandin.

5.6. Immunosuppression

A wide range of immunosuppressive drugs have now been adopted to control unwanted immune responses, particularly those giving autoimmune disease and transplant rejection[49]. The immunosuppressant activity ofM. longifoliawas also explored.Administration of methanolic extract ofM. longifoliato murines was found to decrease the total WBC count and spleen leukocyte count significantly indicating that the extract could suppress the non-specific immune system. Moreover there was a decrement in the relative spleen weight and thymus weight which supports these findings[50,51].

5.7. Anti-hyperglycaemic activity

Diabetes mellitus is a metabolic disorder which is most prevailing problem and is increasing rapidly worldwide[52]. Investigation of Dahakeet aland Seshgiriet al. showed the efficacy of a methanolic extract ofMadhucabark on hyperglycemia[16,53]. Bark extract ofM. longifoliahas shown significant antidiabetic activity in rats indicating its potential role in diabetes treatment and management.The antidiabetic activity may be due to its effect on glucose utilization[16]. Prashanthet al. proved the dose-dependent antihyperglycaemic activity of ethanolic extract of bark at dose 100-200 mg/kg against streptozotocin-induced diabetes in rats[30]. A study by Ghoshet al. showed that the hydroethanolic extract ofMadhucaleaves had significant anti-hyperglycaemic activity against alloxaninduced diabetic rats[39]. The methanolic and ethanolic extracts ofMadhucaseeds also exhibited the antidiabetic activity as studied by Seshgiriet al[53]. The authors postulated that these effects of phytoconstituents may be due to the altering of glucose utilization and insulin level. Thein-vitrostudies showed that extracts also effects the rat intestinal enzymes[54].

5.8. Neuropharmacological activity

Anticonvulsant effect ofMadhucahas also been investigated. It is observed that at a dose of 400 mg/kg there is prolongation the onset of a seizure and also decrease in the seizure duration. It suggests that it may posses an active constituent entity having anticonvulsant nature which may help in the treatment or management of absence seizures. Thein-vivostudy proves the anti-convulsant potential ofMadhucaand thus supports its traditional use as an anti-epileptic agent[38,42].

5.9. Madhuca as anti-neoplastic

Chemoprevention is prominence effect of natural or pharmacological agents on reversing, blocking or delaying the onset of cancer with least adverse effect serving in the reduction of cancer related mortality[55]. Few scientific investigations also showed the chemopreventive action ofMadhucaon human cancer cell lines[56].TheM. longifoliahas also shown the cytotoxic potential against the carcinoma cell.In-vitrocytotoxic assay ofMadhucaagainst the Ehlrichascites, carcinoma cell lines proves its anticancer potential.The crude acetone and ethanolic extract of stem and leaves are used forin-vitrostudy at different dose and showed cytotoxic effect at dose 200 μg/mL. The ethanolic extract showed better potency as compared to acetone extract[37].

5.10. Antihelminthic activity

The antihelminthic activity ofMadhucawas evaluated by incubatingAscardiagalliwith the alcoholic leaf extract. An investigation by Akhilet al. showed that methanolic extracts ofM.longifoliaat a dose of 60 mg/mL showed significant anthelmintic activities when compared to standard drug (Piperazine)[41]. The proposed mechanism by scientist is that it inhibits the glucose uptake and lactic acid content and decreases the glycogen content. Loss of motility was also observed, which may be due to inhibition of energy metabolism or ATP production[57].

5.11. Hepatoprotective and nephroprotective activity

Hepatoprotective effects of the ethanolic extract ofM. longifoliabark was studied based onD-galactosamine induced liver hepatitis.The hepatoprotective effect ofM. longifoliahas been shown in earlier studies. The rise in serum glutamic-oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, and bilirubin levels induced byD-galactosamine administration was significantly reduced[32]. Its hepatoprotective activity might be due to its effect against cellular leakage and loss of functional integrity of the cell membrane in hepatocytes[27,32,33].

5.12. Wound healing

Investigation of Sharmaet al. deduced the notable wound healing property ofMadhucaas compared to standard betadine[31]. This activity may be due to the presence of constituents responsible for the promotion of wound healing. In this study,ether-benzene-95%crude ethanolic extract of leaves and bark ofM. longifoliashowed a marked reduction in wound healing time with respect to control in excision wound model. There was a significant increase in the rate of wound closure and epithelisation rate[31].

5.13. Anti-fertility activity

The crude seeds extract possess antifertility action when administration to male albino rats due to presence of bioactive entity.On administration ofMadhucaseed extract to male albino rats,marked changes were observed proving its effectiveness. It caused weight decrease of testis, epididymis, seminal vesicle, vasa deferens and ventral prostrate which may be due to low plasma level of testosterone. Studies showed that decrease in weight of accessory sex organs was also observed indicating the atrophy of glandular tissue and also reduction in secretory cells thus reflecting the decrease level of testosterone. Thus the seeds ofMadhucahas antifertility potentials in male albino rats[44,45].

6. Toxicity

Toxicity is an important parameter that needs to be evaluated in order to minimize the risk aspect associated with any herbal product.Sometimes plants are used directly or along with the formulated drugs which make it mandatory to access the toxic behaviour of plants. On parenteral administration, saponins are extremely toxic with respect to oral route[58]. The median lethal dose LD50dose of saponin extracted fromMadhucawas found to be 1 000 mg/kg in mice on oral administration. The ethanolic leaves extract ofM.longifoliawere administered at a dose of 175 mg/kg for 14 d to male Wistar rats and morphological and histopathological changes were observed. There were no toxicity effect on liver and kidney upto dose of 2 000 mg/kg. The nontoxic effect of methanolic extract ofM.longifoliabark has also been reported. It was found that bark extract were safe upto the dose level of 2 000 mg/kg[58,59]. However excess dose of mahua oil may lead to antifertility effect as reported by European Food Safety Association. Itsuggest that it causes testicular atrophy and degenerative changes in rats; whereas, no mutagenic or genetic toxicity has been reported in literature till date[60].

7. Non-medical and commercial uses

M. longifolialeaves are also proved as a useful adsorbent. Studies showed thatM. longifolialeaves along with polyaniline adsorbs cadmium and lead from water thus, it can be used for purification.Some studies also reveals the anticorrosive nature of its leaves.It protects the mild steel in 1 mol/L HCl solution from the corrosion[61,62].

Leaves ofM. longifoliaare fed on mothAntracea paphia, which produces Tassar silk, a wild silk used commercially[63]. Flowers are used for distilled liquor preparations[64]. Seeds kernel yields mahua oil which is utilized for cooking and fuel purposes[65].

8. M. longifolia in preclinical and clinical studies

An open clinical trial was performed on 40 subjects with oligospermia to study the efficacy and safety of Chandrakanthi chooram. Chandrakanthi chooram is a formulation consisting of 25 ingredients including flowers ofM. longifolia. The primary outcome of this study was sperm count, its morphology and its motility[66].Clinical studies and surveys onM. longifoliahas also been performed for its anti-venom activity, dyslipidemia in Santhal tribes. The study suggest that regular consumption ofMadhucadrink by Santhal tribes improves their blood sugar and lipid profile[67]. Different parts ofM.longifoliahave been tested preclinically for many pharmacological activities like hepatoprotective, anti-epileptic, antimicrobial,analgesic, and anti-diabetic[6,8].

Kutajarista is one of the ayurvedic marketed products containingM.longifoliawhich is used for the treatment of amoebiasis and bacterial dysentery, amoebic dysentery, and blood diarrhea[68]. Preclinical study of kutajarista was performed in male Sprague Dawley rats and the dose of 40 mL/kg was administered. From the experiment, it was deduced that it cannot be administered for chronic period at higher dose as it will alter the biochemical profile[69].

9. Conclusions

According to scientists, medicines obtained from medicinal plants are best alternative to combat the diseases, as they have immense potential to treat the diseases with least side effect and with high safety and efficacy. They are the strongest contender as alternative treatment and for the adjuvant therapy.M. longifoliais one of most versatile plants which has been used for medicinal as well as to household purposes. All parts of plants had been used in the prevention and treatment of diseases like diabetes and inflammation.Different extracts have been found possessing pharmacological activity. Therefore, it is also termed as “Universal panacea in ayurvedic medicine or Paradise tree for tribals”.

In this review, phytochemistry and pharmacological aspects ofMadhucahas been highlighted. Further exhaustive work is required,because the literature shows limited research in several areas to understand and reveal the mode of its pharmacological activities.In addition, isolation, purification and identification of new entities fromMadhucaspecies are required as it may help further to establish the application of isolated compound in treatment of various acute and chronic diseases and provide more assurance in application of isolated compounds.

Conflict of interest statement

We declare that we have no conflict of interest.

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