Keywords

FormalPara Vernaculars:

Urd.: Bakayen ; Hin. : Bakayen , Dharek , Ghora neem ; San. : Arishta , Himadruma , Mahanimba , Parvatanimba vraksha ; Ben. : Bakarjam , Ghora-nim , Hebbevu , Maha-nimb ; Mal. : Malaivembu , Malai-veppam ; Mar.: Bakana-nimb , Goru-nima , Vilayati-nimb ; Tam.: Kattu vembhu , Malaivembu , Malai-veppam ; Tel.: Konda-vepa , Nimbarun , Turukavepa , Vepa-manu ; Ara.: Habb-ul-ban , Haralshajr , Harbeet , Shajratal-harra ; Chi.: 楝树, Chuan lian , Chuan liang zi , Ku-lian , Kulianpi , Liàn , Tz’u-hua shu ; Cze.: Zederach hladký ; Dan.: Paternostertræ ; Dut.: Galbessen , Kralenboom , Paternosterboom ; Eng.: Cape syringa , Chinaberry tree , Chinese um árbol de los rosarios brella tree , Persian lilac , Pride of India ; Fre.: Acacie d’Égypte , Arbre à chapelets , Azédarach , Cornier des Indes , Faux sycomore , Laurier grec , Lilas de Perse , Lilas des Antilles , Lilas des Indes , Margousier , Patenôtre ; Ger.: Indischer zedrachbaum , Paternosterbaum , Persischer flieder , Zedarachbaum ; Ita.: Albero da rosari , Albero dei paternostri , Albero della pazienza , Perlaro , Sicomoro falso ; Jap.: Sendan ; Kor.: Meol gu seul na mu ; Maly.: Mullayvempu ; Nep.: Bakenu , Khaibasi ; Per.: Aaraatos takhak , Azad derakht , Taghak , Tak , Zanzalakht ; Pol.: Miotla ; Por.: Agrião , Amargoseira , Amargoseira-bastarda , Amargoseira-do-himaláia , Azufeifo , Árvore-santa , Árvore-dos-rosários , Azedaraque , Cinamomo , Falso-sicómoro , Jazmim-de-caiena (Br.), Lilás-das-índias , Mélia-dos-himaláias , Sicómoro-bastardo ; Spa.: Agriaz , Agrión , Árbol de cuentas , Árbol del paraíso , Árbol de los rosarios , Bolillero , Canelo , Cinamomo , Falso sicomoro , Jaboncillo , Lilo de China , Lilo de Persia , Jacinta ; Swe.: Zedrak ; Tag.: Bagalunga , Balgango , Paraiso ; Tha.: Hian , Lian, Lian bai yai ; Tur.: Tesbih ağacı, Tespih ağacı ; Vie.: Cây xoan , Sâ dông.

FormalPara Description:

It is an ornamental deciduous tree often found on street sides in warmer countries, such as India, China, Indonesia, Iran, Syria, Guiana, Madagascar, and Antilles. It grows up to 20 m tall; leaves are long-petioled, two or three-times compound alternate, pinnate, leaflets are dark green above and lighter green below, opposite, glabrous when mature, oval-lanceolate, acuminate, margin irregularly dentate. Flowers grow in clusters, are small, odoriferous, elongate, purple, 1 cm long with five pale purple or liliac petals (April–May); fruit a glabrous drupe, marble-sized, light-yellow at maturity and gradually becoming wrinkled and almost white (September to October).LXXIX Fresh root-bark is thick and rather spongy, the external surface scabrous and warty, of a dark-brown color with irregular ridges; the inner surface is white, taste acrid, nauseous, astringent and slightly bitter.XL It is very similar to neem (Azadirachta indica) except that its fruit pulp is not bitter like that of neem Footnote 1 (Figs. 1 and 2).

Fig. 1
figure 1

Melia azedarach, Leaves, Flowers and Berries, Anna Anichkova, WikimediaCommons; Share Alike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Melia_azedarach_01434.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

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Fig. 2
figure 2

Melia azedarach, Berries, J.M. Garg, WikimediaCommons; ShareAlike 3.0 Unported CC BY-SA 3.0, https://commons.wikimedia.org/wiki/File:Indian_Grey_Hornbill_(Ocyceros_birostris)_eating_Bakain_(Melia_Azadirachta)_berries_at_Roorkee,_Uttarakhand_W_IMG_9016.jpg; https://creativecommons.org/licenses/by-sa/3.0/deed.en

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FormalPara Actions and Uses:

It is one of the most commonly used plants for various diseases, especially skin diseases, by tribal people throughout the world [1, 7, 35, 46]. Fresh leaves boiled in water are used by women to grow and strengthen their hair.LXIX The plant has deobstruent, resolvent and alexipharmic properties. Flowers and leaves are applied as poultice to relieve nervous headaches, and internally, the leaves’ juice is administered as anthelmintic, antilithic, diuretic and emmenagogue, and is thought to resolve cold swellings, and expel the humours which give rise to them. The bark and leaves are used externally and internally in leprosy and scrofula.XXI,LXXXI,CV A poultice of flowers kills lice and cures eruptions of the scalp. The fruit is poisonous, but nevertheless is prescribed in leprosy and scrofula, and is worn as a necklace to avert contagious diseases. The root bark has a bitter, nauseous taste and yields its virtues to boiling water. One hundred ten (110 g) of fresh bark boiled in about a liter of water until the volume was reduced to half; the dose for a child was one tablespoonful every three hours until the bowel and stomach were cleared, or twice daily for several days followed by a cathartic.XL Unani physicians describe it as blood purifier, analgesic, antihemorrhoidal, wound healer, anthelmintic, antipyretic for chronic fevers and antiperiodic; and use the leaves and bark in diseases like leprosy and leucoderma, and externally the leaves decoction for fomentation and poultice for boils and sores. Bark decoction is used to kill and expel intestinal worms.LXXVII Externally, the seed oil is used as an antiseptic for indolent sores and ulcers, for rheumatism and skin diseases such as ringworm and scabies, and internally, the oil is used in malaria fever and leprosy [28], as antidiabetic, spermicidal, and antifertility agent [44]. Leaves juice is also used in the Philippines as anthelmintic, antilithic, diuretic and emmenagogue.CXVII The flowers, leaves and fruits are recommended in Iranian traditional medicine as a remedy to normalize temperament in elderly, for brain obstruction, intestinal worms, kidney stones, leprosy, vitiligo, purulent sores, as an antidote to toxins, diuretic, emmenagogue, hair growth inducer and to kill lice [25]. Fruit powder is insecticide against flies,LXXXVIII and the root is considered anthelmintic by Ethiopians [31],LXXIX while the bark was considered vermifuge in the Philippines.LVI In Indo-China, seeds were recommended for typhoid fever and retention of urine [17]. The root bark was included in the official Pharmacopoeias of the United States and Mexico.XV In traditional Chinese medicine, it is used orally and topically as an antiparasitic and antifungal agent [40]; the roots and barks of M. azedarach and M. toosendan are known as Kulianpi ; and are described as bitter, ‘cold’ and slightly toxic. They are indicated for the treatment of ascariasis, oxyuriasis, erysipelas, rubella, scabies and tinea favosa. Powdered Kulianpi , mixed with vinegar is used externally for scabies.XVIII

FormalPara Phytoconstituents:

A series of limonoids, triterpenes, steroids and flavonoids and limonoid glycosides, including salannin, meldenin [49, 50], melianoninol, melianol, melianone, meliandiol, vanillin, vanillic acid [22, 32, 48], 3-deacetyl-4′-demethylsalannin, 3-deacetyl-28-oxosalannin, and 1-detigloylohchinolal [38], ring C-seco limonoids [63, 64], lignanes: pinoresinol, bis-epi-pinoresinol, hemicetal and diacid [11], and tirucallane triterpenoids [2, 62] have been isolated from the fruits. Steroids [56], triterpenoids and sterol [61], and flavonoid glycosides, including quercetin 3-O-rutinoside, kaempferol 3-O-robinobioside and kaempferol 3-O-rutinoside [30] have been isolated from the leaves. Triterpenoids, steroids [21, 57]; limonoids, and sesquiterpenoid [58] have also been isolated from the bark. Azadirachtin-type limonoids, meliacarpinin D, melianin B, highly cytotoxic sendanin-type limonoids [19, 20, 24, 52], and trichilin-type limonoids, including meliatoxin B1, trichilin H, trichilin D and 1,12-diacetyltrichilin B [53] have been reported from the root bark. Chemical constituents of the seeds include β-sitosterol, vanillin, benzoic acid, vanillic acid, daucosterol, α-d-glucopyranose, limonoid glycosides: 6,11-diacetoxy-7-oxo-14β,15β-epoxymeliacin (1,5-diene-3-O-β-d-glucopyranoside) and scopoletin, melianol, meliacin, meliacarpin, meliartenin hydroxyl-3-methoxcinnamaldehyde and (+-) pinoresinol [12, 13]. Kulianpi is reported to contain toosendanin, margoside, kaempferol, resin, tannin, n-triacontane, β-sitosterol, and the triterpene kulinone. Seeds yield 60% of a fatty oil comprising stearic, palmitic, lauric, valerianic, and butyric acids, and traces of a sulfurated essential oil.XVIII

FormalPara Pharmacology:

Methanol flower extract healed S. aureus caused skin infection in rabbits, an effect that was comparable to neomycin [47]. The fruit extract showed higher antibacterial effect against Gram-negative bacteria, while the leaf extract was more effective on C. albicans [37]. Various bark extracts have shown significant antibacterial activities against a number of pathogenic bacteria [59]. Fresh green leaves extracts contain an antiviral factor that inhibits replication of several animal viruses [5, 18, 54, 55], protects neonatal mice against Tacaribe virus inoculation-induced lethal encephalitis, and protects offspring of nursing mothers from developing viral encephalitis [6]. Meliacine is identified as the compound possessing antiviral activity that inhibits HSV-1 replication [3], exerts a strong antiviral action on corneal HSV-1 inoculation in mice [4, 10, 41], and has a protective effect against genital herpetic infection in mice [39]. Hydroethanol leaf extract showed pediculicidal activity, killing all lice faster than 1% permethrin [45]. Ethanol leaf extract also possesses significant in vitro radical scavenging activity, and protects cells against oxidative damage [34]. Hexane leaf and seed extracts exhibited significant antipyretic activity in rabbits, comparable to aspirin [23, 29].

Ethanol leaf extract in a dose of 100 mg/kg daily for 21-days caused complete loss of libido in male rats [14], and ethanol root extract and its chloroform fraction interrupted pregnancy in 75% of female rats [26, 27]. Seed extract also increases preimplantation, post-implantation and total prenatal mortalities during early and late stages of gestation in rats [33]. However, 50% ethanol and acetone extracts of leaf showed no anti-implantation activity in rats [42]. The fruit extracts showed activity against tapeworms and hookworms better than piperazine phosphate and hexylresorcinol, respectively [51]. Methanol extracts of leaves and seeds are strong larvicidal, pupicidal, adulticidal, and repellent to mosquito [15, 36], so is the hydroalcohol extract of the leaves [43]. Aqueous leaf extract showed strong anticomplementary activity, but did not affect phagocytic activity of PMNL [9]. Treatment of mice with the aqueous extract diminished production of antibodies and inhibited graft vs host and delayed type hypersensitivity reactions [16].

FormalPara Human A/Es, Allergy and Toxicity:

Melia azedarach pollens have been reported to cause respiratory allergy [8]. Eating fruits is described as a fatal poison; causes vomiting, asphyxation, dizziness, coma and death. Consumption of six to nine fruits, 30–40 seeds, or 400 g of the bark are considered toxic to human in Chinese medicine. Poisoning may cause gastrointestinal, cardiovascular, respiratory, or neurological effects; general weakness, myalgia, numbness, and ptosis are the presenting symptoms, which may occur within 4–6 h after ingestion [40]. Children have died from eating berries and adults from making a brew out of leaves. A resinous poison is in the fruit-pulp, but the amount varies with the strain and growing conditions. Irritant activity of the plant is evident in causing vomiting and constipation or diarrhea. Difficulty in breathing, weakening heart activity, and nervous depression or excitement and paralysis may develop. Symptoms may occur for several hours and death may take place within a few days.CXXXV The epiderm of the bark is more toxic and should be discarded.

FormalPara Animal Toxicity:

Oral administration of aqueous and alcoholic extracts of flowers and berries caused mild CNS depression but were nontoxic up to a dose of 1,500 mg/kg in mice and rats. Intravenously, LD50 of aqueous extract of berries in mice and rats were 700 and 925 mg/kg, respectively; and of flowers extract 395 and 580 mg/kg, respectively [60].

FormalPara Commentary:

Despite many clinical uses in traditional medicines, no RCTs are reported in the published literature, except from China on fresh Kulianpi decoction being very effective against ascariasis infestation in both adults and children.XVIII