NEEM TREE (Azadirachta indica) - AN ELIXIR IN ORAL CANCER

Neem tree has been used for hundreds of years to treat oral diseases, we tend to evaluated its effects against OSCC because it relates to inflammation-driven tumorigenesis.

BOTANICAL DESCRIPTION OF NEEM TREE 

Azadirachta indica, or Neem, belongs to a family of trees regarding mahogany; meliaceae.  

Neem, a tropical tree within the Indian sub-continent has been used for its healthful properties in the Ayurvedic drugs for over 4000 years. 

Neem was described by De Jussieuin 1830 and its taxonomic classification is as follows:

Kingdom: Plantae 
Division: Magnoliophyta
Class: Magnoliopsida
Subclass :Rosidae
Order: Sapindales
Family: Meliaceae
Genus :Azadirachta
Species: Azadirachta indica

Neem ingredients are applied in Ayurveda, Unani, Homeopathy, and modern drugs for the treatment of the many infectious, metabolic, or cancer disease. 

Plant elements have compounds that demonstrate potential within the fields of drugs, post-management, environment protection. 

The native supply of eco-friendly agrochemical, pesticides, and pesticides is that the Azadirachta indica. 

It is a part of India’s wealthy genetic diversity. 

In the world, there have been several researches done on this tree and it's thought-about to be a reliable tree of the twenty first century. Azadirachta indica is variable to a far-range of topographical, edaphic factors, and climate. 

It thrives alright in stony, dry, shallow soils and conjointly on soils having onerous clay pan, at a shallow depth. 

It needs lots of daylight and small water. Within the vary of 450-1200 millimeter rain tree grows well in these areas. 

However, wherever the rain is as low as 150-250 millimeter neem tree trees has been introduced even in these areas. 

Neem tree grows on altitudes up to 1500 m . In wide, temperature vary of 0-49°C Azadirachta indica trees were grownup. 

Poorly drained soils and water-logged areas cannot combat by Azadirachta indica trees. 

A suitable pH scale vary lies in between four and ten for the expansion of tree. 

Acidic soils are neutral in a very distinctive method with the property of calcium mining of tree.

Neem is native to india, Myanmar, Bangladesh, Sri Lanka, Malaysia, and Asian country and grows in tropical and semi-tropical regions round the world

The neem could be a supply of extremely active liminoid terpenoids, together referred to as azadiractoids that are shown to own antineoplastic activity

                       Neem leaves

                          Neem tree

ACTIVE COMPONENTS OF NEEM

GENOTOXICITY PROPERTY OF NEEM

Genotoxicity could be a property of chemical agents that damages the genetic data at intervals a cell inflicting mutations, which can cause cancer. 

The chemicals used has harmful effect on cell’s genetic material i.e. deoxyribonucleic acid and ribonucleic acid, that affects the integrity of the cell.

The permanent, hereditary changes will have an effect on either somatic cells of the organism or germ cells to be passed on to future generations.

The genotoxic substance invades the nucleus and causes injury to the nucleic acid and also the changes is viewed by desoxyribonucleic acid fragmentation.

Neem oil shows genotoxicity on the oral cancer cells by degrading ITS desoxyribonucleic acid,Hence neem oil has the potential to be associated degree anti-cancerous drug.

Neem tempered with different natural compounds is also of nice promise in Finding a positive cure for cancer patients and may be accustomed create more scope within the discovery of chemopreventive drugs.

Damage to the DNA

Photo credit: https: www.clinicalomics.com

EFFECT OF NEEM IN APOPTOSIS 

Bcl2 and bax play a crucial role within the regulation of apoptotic process. Any alteration in bcl2 and bax causes the development and progression of tumours

Leaf extract downregulated Bcl-2 expression and upregulated Bim, caspase-8, and caspase-3 expression within the buccal pouch indicating that it's cell death causing effects in the target organ

Neem show a spread of activities affecting multiple targets and additionally play role within the induction of apoptotic death in cancer 

                     Effects of neem

EFFECT OF NEEM IN TUMOURS SUPPRESSION GENE 

p53 is a crucial tumor suppressor gene and it plays role within the inhibition of the proliferation of abnormal cells, in this means inhibiting the development and progression of cancer. 

A study confirmed that ethanolic fraction of neem tree leaf (EFNL) treatment effectively upregulated the proapoptotic genes and proteins together with 

• p53
• Bcl-2-associated X protein (Bax)
• Bcl-2-associated death promoter protein (Bad) caspases
• pTEN
• c-Jun N-terminal enzyme (JNK). 

A finding showed that ethanolic neem tree leaf extract increased the expression of 

• proapoptotic genes
• resembling caspase-8 and caspase-3
• suppressed the expression of Bcl-2 and mutant p53 within the 7 ,12-dimethylbenz[a]anthracene-induced cancer cells .

Nimbolide, a tetranortriterpenoid limonoid, is one in all the necessary contributors to the toxicity of neem tree extracts. 

Nimbolide downregulated cell survival proteins, together with I-FLICE, cIAP-1, cIAP-2, Bcl-2, Bcl-xL, survivin, and X-linked matter of programmed cell death macromolecule, and upregulated the proapoptotic proteins p53 and Bax.

Oral squamous cell carcinoma induced by 7,12-dimethylbenz[a]anthracene is suppressed by aqueous neem leaf extracts is exhibited by decreased occurrence of neoplasm. 

EFFECT OF NEEM ON NF-κB  TRANSCRIPTION FACTOR

The NF-κB transcription factor plays a serious role in cancer and connected diseases. Inhibition of NF-κB action may be a very important step within the interference of cancer development and progression. 

Curcumin, leaf extract, and raspberry extract (RSE) considerably inhibited both constitutive and RT-induced NF-κB. 

ANTI-INFLAMMATORY ACTION OF NEEM (SCNE) IN OSCC

 Salivary levels of IL-6, IL-8, IL-10, and TNFα are all raised in patients with malignant OSCC and so are projected to be discriminative biomarkers for oral cancer with IL-6 being related to poor response to therapy and poor prognosis.

 
These studies powerfully recommend that chronic inflammation potentiates the progression of OSCC 

SCNE was evaluated for antiproliferative, anti-inflammatory, and antimetastatic potential in vitro and in vivo exploitation cell based mostly assays. 

Effects on circulating cytokines, inflammatory markers, and apoptotic markers are demonstrated; specifically dramatic downregulation of TNFα, IL-6, and downstream modulator STAT3 expression and activity are incontestible. 

This inflammatory inhibition provides a possible mechanism for the preventive and therapeutic efficaciousness of SCNE against OSCC

IFNγ is a crucial protein created in many response cells such as natural killer, natural killer T cells, and activated T cells, this method may be helpful in adaptive antitumour immune response 

PROPERTIES OF SCNE IN ORAL MALIGNANCY 

Jay Morris and his fellow researches done research in The Highly Pure Neem Leaf Extract, SCNE, Inhibits Tumorigenesis in Oral Squamous Cell Carcinoma via Disruption of Pro-tumorInflammatory Cytokines and Cell Signaling thus the result as follows 

• Chemopreventive effects of SCNE derived from a natural supply with ethnopharmacological properties, on OSCC tumorigenesis.

• SCNE conjointly considerably reduced cell migration, suggesting the potential to inhibit metastasis.

• SCNE on the inflammatory signal cascade via downregulation of NFkB, STAT3, and COX2 expression and/or activity in OSCC cell lines.

• The SCNE diet in xenograft models (mouse) evaluated therapeutic effects on tumour growth and 4NQO-1 carcinogen-induced model evaluated hindrance of tongue lesions such as dysplasia and OSCC

• SCNE promotes an antitumour composition that's not dependent upon T-cell activity, however is also increased by a completely competent immune status.

• SCNE anti-inflammatory effects and reduction in NFkB/STAT3 axis, there's potential for future studies to measure the synergistic effects of SCNE together with standard platinum-based chemotherapies and radiotherapy to treat OSCC and cut back recurrence rates and mortality.

CONCLUSION 

Popularity of natural products or their derivatives role in diseases cure and prevention is increasing worldwide because of less side effect properties. 

The role of active ingredients as chemopreventive result has been noticed  in various tumour via modulation of various cell communication pathways.

Further advanced analysis with neem is extremely useful for patients littered with carcinoma. 
Neem as associate antineoplastic drug is doubtless required to scale back the devastating worldwide consequences of malignancy.

REFERENCE 

• Morris J, Gonzales CB, De la Chapa JJ, Cabang AB, Fountzilas C,Patel M, Orozco S and Wargovich MJ (2019) The Highly Pure Neem Leaf Extract, SCNE, Inhibits Tumorigenesis is in Oral Squamous Cell Carcinoma via Disruption of Pro-tumor Inflammatory Cytokines and Cell Signaling. Front. Oncol. 9:890. doi: 10.3389/fonc.2019.00890
• Mohammad A. Alzohairy, Therapeutics Role of Azadirachta indica (Neem) and Their Active Constituents in Diseases Prevention and Treatment. Volume 2016, Article ID 7382506   https://doi.org/10.1155/2016/6
• T. Priadarsini, Vishnupriya, Gayathri R Gentotoxicity Analysis of Neemoil on Oral Cancer Cell Line by DNA Fragmentation. Int. J. Pharm. Sci. Rev. Res., 39(1). 
• Trivedi A, Fatima N, Husain I, Misra A. An Update On The Therapeutic Potential Of Neem And Its Active Constituents: A Panacea For All Diseases. Era J. Med. Res. 2019; 6(1): 1-8.
• Himanshu deswal, Yogender Singh, H.S.Grover, Amit Bhardwaj, Shalu Verma. Neem: A boon in medical and dental therapies: A review. Vol 4, Issue 2, 2016. ISSN - 2321-6832
• Oral cancer picture taken from https://www.researchgate.net/figure/a-Oral-squamous-cell-carcinoma-in-the-floor-of-the-mouth-conventional-white-light_fig3_325996651