Introduction

The plant products or natural products show an important role in disease prevention and treatment through the enhancement of antioxidant activity, inhibition of bacterial growth, and with modification of genetic pathways. Neem is one of the indigenous medicinal plants of India which possesses medicinal properties in every part viz., roots, seeds, flowers, bark, leaves, fruit pulp, etc. Each of the plant part has been used in the Indian Ayurvedic and Unani systems of medicine and has become a cynosure of modern medicine. Indians have long valued the Nimba tree; for centuries, millions have cleaned their teeth with Nimba twigs, smeared skin disorders with Nimba-leaf juice, taken Nimba tea as a tonic, and placed Nimba leaves in their beds, books, grain bins, cupboard, and closets to keep away troublesome bugs.

In Ayurvedic literature Neem is well known for its medicinal properties viz., Neem bark is cool, bitter, astringent, and acrid. In addition to this, it is used to cure tiredness, cough, fever, loss of appetite, worm infestation etc. It also heals wounds and vitiated conditions of Kapha, vomiting, skin diseases, excessive thirst and diabetes. Its fruits are bitter, purgative, anti-haemorrhoids and anthelminthic.^[1]

This tree is an incredible plant that has been declared the “Tree of the 21st century” by the United Nations. The importance of the Nimba tree has also been recognised by the US National Academy of Sciences, which published a report in 1992 entitled ‘Neem-a tree for solving global problem.^[2]

This review summarises the role of Neem and its 5 parts along with their active constituents in disease prevention and treatment.

History

The earliest authentic record of the curative properties of Neem and its use in the indigenous system of medicine in India is found in Kautilya’s "Arthashastra" around the 4^th century BC. Ayurvedic texts in Sanskrit describe neem as ‘Sarva Roga Nivarini’ - (the universal healer or curer of all ailments), ‘Arishtha’ (perfect, complete, and imperishable), and ‘Nimba’ from the term ‘Nimbati Syasthyamdadati’ which means ‘to give good health’.

Figure 1B: Bark

Figure 1C: Fruits of Neem

Table 1: Taxonomic classification of Azadirachta indica (Neem)

Therapeutic uses of Panchnimba

1. Neem leaves

Leaves are applied as poultices to relieve boils, ringworms, eczema, ulcers, itching, and other skin diseases. Paste of the leaves is used in case of acne vulgaris. Their infusion is used as an antiseptic wash to promote the healing of wound and ulcers. Leaves are useful for chickenpox, reduce fever caused by malaria, treat various foot fungi, and cure neuromuscular pains.^[37] Leaf juice is given in gonorrhoea and leucorrhoea. The leaf's fresh juice is administered with salt to treat intestinal worms. The aqueous extract of leaf shows potent immuno-stimulant activity as evidenced by both humeral and cell-mediated responses. The wound-healing property of leaf extract is also validated in animal models of rats with excisional and incisional wounds. Early research recommends that applying a gel containing neem leaf concentrate to the teeth and gums twice day by day for about a month and a half may lessen measure of plaque on teeth.^[38]

2. Neem bark

The bark is used as a bitter tonic, astringent, antipyretic, against nausea and vomiting.

Extrapharmacopiel uses

1. Neem leaves

• Neem leaves are used as green leaf manure and also in the preparation of litter compost.^[40]
• Neem leaves are also used in the storage of grains.
• Leaves due to insecticidal properties are kept with woollen and other clothes for a long time.

2. Neem seed cake

Neem seed cake performs the dual function of both fertilizer and, pesticide, acts as a soil enricher, reduces the growth of soil pest and bacteria, provides macronutrients essential for all plant growth, and helps to increase the yield of plants in the long run, biodegradable, Eco friendly and excellent soil conditioner.^[41]

3. Neem bark and roots

Bark & roots in powdered form are also used to control fleas & sucking pests in rice cultivation.

Pharmacological profiling on Panchnimba

1. Neem leaves

Hepatoprotective effect

Aqueous neem leaf extract (ANLE) showed hepatoprotection against anti-tubercular drug-induced damage in rats as indicated by minimized alteration of bilirubin, Alanine aminotransferase, Aspartate aminotransferase, and Alkaline phosphatase in serum. Azadirachtin-A, and, Nimbolide the major components of neem, showed a hepatoprotective effect against carbon tetrachloride (CCl4)-induced liver injury in rat models with efficacy similar to that of Silymarine standards.^[42]

Anti diabetic effect

Neem leaf extracts showed promising results in decreasing blood sugar level and prevents adrenaline as well as glucose induced hyperglycaemia. Recently, hypoglycaemic effect was observed with leaf extract and seed oil in normal as well as alloxan-induced diabetic rabbits.^[43]

Immunostimulant effect

The aqueous extract of leaf also possesses potent immune-stimulant activity as evidenced by both humoral and cell-mediated responses.

Also, three tricyclic Diterpenoids, Margolone, Margolonone and Isomargolonone isolated from stem bark of Nimba were found to be active against Serratia species, Klebsiella, and Staphylococcus which shows its antimicrobial property.

Immuno-stimulant activity

The aqueous extract of bark of Azadirachta indica showed anti complimentary activity, acting on both classical pathway activation and alternative pathway activation.^[51]

Antiulcer

Neem bark extract reduced human gastric acid hypersecretion, and gastro-oesophageal and gastroduodenal ulcers. After 10 weeks, the duodenal ulcers were nearly fully healed; after 6 weeks one case of oesophageal ulcer and gastric ulcer were fully healed.^[52]

Anti-microbial activity

The bark extract exhibited significant antimicrobial activity on Pseudomonas aeruginosa, Proteus mirabilis and Enterococcus faecalis at all the concentrations tested, whereas its antimicrobial activity on Staphylococcus aureus, Aspergillus fumigates and Candida albicans was observed at higher concentrations (>500µg/ml).^[53]

5. Neem root

Antidiabetic activity

A study was undertaken to evaluate the 70% alcoholic neem root bark extract (NRE) in diabetes and results showed that neem root bark extract showed statistically significant results in 800mg/kg dose.^[54]

Free radical scavenging activity

Qualitative chemical analysis of root bark extract showed the presence of saponins, flavonoids, and terpenoids. The root bark hydro alcoholic extract of Azadirachta indica exhibited significant free radical scavenging activity as determined by DPPH (2, 2 Diphenly 1 picryl hydrazyl solution (DPPH) assay and total antioxidant activity.^[55]

Important Preparation

There are various preparations from parts of the neem such as Fruits, Leaves, Roots, Bark, flower,

• Panchtikta Ghrita Guggul

are responsible for its anti-inflammatory, anti-microbial activity, anti-diabetic and anti-cancerous property. It also possess hepatoprotective, anti-fertility, immunostimulant, anti-ulcer, & antimicrocidal activity. The use of neem is not just limited to its single part but each part has been used extensively since time immemorial. In Ayurveda, many Nighantus have mentioned the Panchnimba or its five useful parts along with their Ayurvedic pharmacodynamics. Leaves having Katu Vipaka it pacifies the Pitta Dosha and it possess Krimi-Vishahra property, Netraya and Ruchikara. Unriped fruit showed Kushth-Krimihara actions due to its Tikta Rasa, Ushna Virya and Katu Vipaka. It cures Gulma and Arsh because of its Laghu Guna, Tikta Rasa and Ushana Virya. Whereas riped fruit possess Raktapitthara property because of its Tikta Rasa which purifies blood, it has bitter taste, it improves the digestive fire. Due to Katu Vipaka, Flower of the neem alleviates Pitta Doshas and vitiate Vata Doshas.

Ayurvedic Pharmacodynamics reveals that although neem itself is Sheet Virya but its fruits in Apakwa Awastha and Pakwa Awastha are Ushna Veerya. Also, the fruit has Madhur and Tikta Rasa whereas neem has Tikta and Kashaya Rasa.

Conclusion

Neem and its active bio constituents have therapeutics implications and have been traditionally used worldwide especially in Indian subcontinent since ancient times. People used neem at home as remedy they apply the leaves paste on their face and bark of the stem on any kind of wound or on skin disorders. It can be easily available and not as much expensive as comparison to other modern medicine. Neem has commercial and high economic importance used as a bioavailability enhancer can be explored in various formulations. All parts of the neem are useful for various body ailments. Also, it is helpful to relieve excessive thirst, it is helpful in relieve cough, it is useful in fever. It is very helpful in relieve from anorexia. Neem is useful in intestinal and other worms, also helpful to heal wounds and cleans the wounds. It is very useful in vomiting and nausea, also helpful in various skin disease also helpful in diabetes and urinary tract related infection. So, it can be concluded that neem heals the various ailments of the body. From Samhita time to modern era neem is an important, always available, economical,