Neem (Azadirachta indica, Meliaceae) is one of the most versatile and useful medicinal plants ever discovered. Each one of its parts is rich in bioactive compounds that are traditionally used for treating various conditions. Research has shown that the neem tree’s bioactive compounds, including nimbolide, azadirachtin and gedunin, play an important role in the regulation of biological processes, both in vitro and in vivo.
A tree with miraculous powers
Neem predominantly grows in India and the neighbouring countries of the Indian subcontinent, where it has been used as a medicinal plant for more than 4500 years. According to available sources, neem is the first medicinal plant that became a part of traditional Siddha medicine, which is believed to be the oldest existing medical system in the world. Throughout history, different specimens of neem trees have apparently shown to be extremely effective when it came to treating many different sorts of pain, infections, fevers and other ailments – so effective, in fact, that the plant itself has been dubbed the village pharmacy. At the beginning of the twentieth century, Indian colonizers and settlers spread neem trees all around the world. Nowadays, this marvellous plant is of great medicinal value in both modern medicine and alternative medical practices such as Ayurveda, Unani and homeopathy.
Active ingredients of the neem tree and their mechanism of action
Over a thousand scientific articles have confirmed that the neem tree contains more than 300 structurally unique ingredients. Chemical compounds detected in neem trees can be split into two main groups: isoprenoids and non-isoprenoids. The non-isoprenoid group includes proteins, polysaccharides, polyphenols, coumarin, organosulphur compounds, dihydrochalcone, aliphatic compounds and tannins. The isoprenoid group can be split further into diterpenoids and triterpenoids. The main bioactive substances of the neem tree belong to the triterpenoid group of compounds. More accurately, they belong to the triterpenoid group’s limonoid subclass. While new types of neem limonoids are currently being discovered, azadirachtin, salannin, meliantriol and nimbin seem to be the most significant ones for now.
Biological activities of the neem tree and its compounds
It has been shown that the neem tree and its components play a role in modulating multiple cellular signalling pathways. Depending on the exact goal and the conditions inside the cell, such pathways can be regulated in two directions: upwards and downwards. The most common targets include transcription factors, enzymes, growth factors, cytokines, kinases, receptors and proteins involved in the processes of cell proliferation, apoptosis and metastasis.
- acts as an antioxidant, mostly owing to its high polyphenol content and to its compounds azadirachtin and nimbin.
- displays anti-inflammatory properties, which are attributed to its limonoids that can significantly reduce both the amount of released pro-inflammatory cytokines and prostaglandins, and the immune response as a whole by inhibiting cellular signalling pathways (e. g. through the κB nuclear factor).
- also has antiangiogenic properties due to the presence of the so-called neem leaf glycoprotein (NLGP), which displays the ability to reduce the growth factor of vascular endothelial cells and normalise the vascular tone. Such antiangiogenic properties were also observed in the presence of other related compounds, most notably nimbolide, nimbolinone and the derivatives of salannol and nimbinene.
- also acts as an immunomodulator, which is proven by the increase in the total number of CD4+ and CD8+ lymphocytes and monocytes. The compounds gedunin, nimbin and NLGP have a mediating effect in this process of immunomodulation.
- contains limonoids that display apoptotic properties; most notably nimbolide, which is why it is being tested as a drug of interest in cancer treatment.
The medicinal uses of neem
Neem is mainly used today as an antiseptic agent against a wide spectrum of pathogens, including fungi, bacteria and viruses. This usage of neem and its medicinal preparations is the most supported one by the available scientific evidence. Herbal preparations containing neem are apparently effective against many different skin diseases, wounds, infected burns and periodontal disease. There are promising indications that neem could be used on a much wider scale in the future due to its influence on numerous biological pathways. The aforementioned biological activities of the compounds found in neem trees point to its potential use as an anti-inflammatory substance, analgesic, antipyretic, antiparasitic, antihypertensive, antiulcerant, antidiabetic, a cytostatic and a contraceptive.
Handling herbal preparations should be done with caution due to the many different components that may be coextracted during the preparation process and the contaminants that may find their way into the prepared mixture itself. However, that does not mean that further research into efficient extraction methods, active components and synthetic structurally similar compounds should be completely stopped. More than 70% of medications available today were first synthesised by studying similar products derived from natural sources. Multiple studies conducted on neem extracts show that neem could be used in the development process of new effective drugs as well.
Neem as a green pesticide
Many entomologists (zoologists who study insects) believe that neem is the future of safe and natural pesticides because it affects many different species of harmful insects, while remaining safe for humans, other animals and useful insects. Neem-based pesticides are also biodegradable and resistant to protective genetic factors of different sorts of vermin.
Neem trees contain a few active ingredients that produce different effects in different surroundings. These compounds are not similar in any way to the chemicals commonly found in synthetic insecticides. They are distantly chemically related to steroidal compounds, therefore, they only consist of carbon, hydrogen and oxygen atoms. They lack chlorine, phosphorus and nitrogen atoms commonly found in contemporary synthetic pesticides; that is precisely why they produce a completely different effect. Neem’s uniqueness lies in the fact that it does not kill directly. In fact, it changes either the behaviour of insects or their internal life processes in ways that can be very subtle. An affected insect cannot mature, reproduce or feed on plants anymore, which prevents it from causing further damage on crops.
Neem – the tree of the 21st century 
2 National Research Council (US) Panel on Neem. Neem: A Tree For Solving Global Problems. Washington (DC), National Academies Press US, 1992
3 Gupta SC et al. Neem (Azadirachta indica): An indian traditional panacea with modern molecular basis. Phytomedicine, 2017, 34, 14-20
4 Neem, The UN’s tree of the 21st century. Nairobi, United Nations Environment Programme, http://www.unep.org/, retrieved 16 January 2022
5 Kharwar RN et al. Harnessing the Phytotherapeutic Treasure Troves of the Ancient Medicinal Plant Azadirachta indica (Neem) and Associated Endophytic Microorganisms. Planta Med., 2020, 86, 906-940
2 Drawn using https://molview.org/
3 Kharwar RN et al. Harnessing the Phytotherapeutic Treasure Troves of the Ancient Medicinal Plant Azadirachta indica (Neem) and Associated Endophytic Microorganisms. Planta Med., 2020, 86, 906-940
4 Gupta SC et al. Neem (Azadirachta indica): An indian traditional panacea with modern molecular basis. Phytomedicine, 2017, 34, 14-20
5 Drawn using https://molview.org/
6 Guddanti, Pixabay