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 Table of Contents  
REVIEW ARTICLE
Year : 2016  |  Volume : 28  |  Issue : 1  |  Page : 17-23

Therapeutic aspects of Tulsi unraveled: A review


1 Department of Oral Medicine and Radiology, P.M.N.M. Dental College and Hospital, Bagalkot, Karnataka, India
2 Private Practice, Bagalkot, Karnataka, India
3 Department of Oral Medicine and Radiology, Kalinga Institute of Dental Sciences, Bhubaneswar, Odisha, India

Date of Web Publication8-Sep-2016

Correspondence Address:
Naveen Srinivas
Department of Oral Medicine and Radiology, P.M.N.M. Dental College and Hospital, Bagalkot, Karnataka - 587 101
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-1363.189984

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   Abstract 

Introduction: The purpose of the paper was to review the diverse pharmaceutical aspects of Tulsi. Materials and Methods: Several publications and books were electronically searched in google using the keywords “Tulsi as a medicine,” “Tulsi as a medicinal plant,” “Medicinal properties of Ocimum sanctum,” and “Tulsi in dentistry.” The search was limited to articles and books in the English literature. To prepare a thorough review on the therapeutic aspects of Tulsi, the contents were screened between the year 1985 to 2015 by going through the title and abstracts, and further shortlisting articles for full text reading. Conclusion: The present review revealed that Tulsi has an extensive array of medicinal uses, as evidenced by various studies conducted, but its use in allopathic medicine is still limited because of the lack of clinical trials on humans.

Keywords: Medicinal plant, Ocimum sanctum, herbal medicine


How to cite this article:
Srinivas N, Sali K, Bajoria AA. Therapeutic aspects of Tulsi unraveled: A review. J Indian Acad Oral Med Radiol 2016;28:17-23

How to cite this URL:
Srinivas N, Sali K, Bajoria AA. Therapeutic aspects of Tulsi unraveled: A review. J Indian Acad Oral Med Radiol [serial online] 2016 [cited 2019 Nov 12];28:17-23. Available from: http://www.jiaomr.in/text.asp?2016/28/1/17/189984


   Introduction Top


Plant kingdom is known to comprise approximately 500,000 plant species which are found worldwide, of which only 1% has been phytochemically investigated with an illimitable potential for discovering novel bioactive compounds mainly in medicinal plants. Use of traditional plants and their products have been reported by various investigators for the treatment of diseases.[1] Despite the ever increasing advancement in medical sciences and molecular diagnosis, it is estimated that 80% of the world population is still dependent on plant-derived pharmaceuticals.[2]Various plants are used for manufacturing of drugs which include: Morphine (derived from Papaver somniferum), Ephedrine (derived from Ephedra vulgaris), Aswagandha (derived from Withania somnifera), Atropine (derived from Atropa belladonna), and Reserpine derived from (Roulphia serpentina).[3],[4] Such plants that have medicinal properties are known to comprise of essential oils which are therapeutic in nature. Importance of having such medicinal plants for therapeutic uses is that they are economical, effective and easily available, thus, making them useful tools for the medical practitioners to treat their patients.

Ocimum sanctum L. is one such medicinal plant having numerous medicinal properties.[3],[4]O. sanctum L. (syn O. tenuiflorum L., Mint family: Lamiaceae), commonly known as “Holy Basil” in English and “Tulsi” in Hindi and Sanskrit, is a bushy plant with a unique fragrance found in the semitropical and tropical regions of the world.[5] In ancient Hindu scriptures, Tulsi occupies the supreme position among the herbs, so much so that it is referred to as “Mother.” The ancient works of Padmapurana and Tulsi Kavacham describes Tulsi as a protector of life, accompanying human beings from birth to death. The ancient sages or rishis ensured its integration into daily life by incorporating it in religious rituals.[6]

This plant is grown all over India for its medicinal as well as for religious purposes in houses, temples and gardens. It is also grown on commercial basis in vast stretches of farmlands to cater to herbal, cosmetic, and pharmaceutical industries. The medicinal uses of Tulsi is well-documented and is extensively used in the Indian traditional systems of medicine, that is, Ayurveda, Unani, Siddha, and the Asian folk medicine in India, Nepal, SriLanka, Malaysia, Indonesia and Burma for treating various diseases either alone or in combination with other herbal plants.[7] Tulsi has been used for thousands of years for its diverse healing properties and is regarded in Ayurveda as the “elixir of life” that promotes longevity.[8]

Morphological types

Commonly, there are three types of Tulsi, one with a purple-colored leaf or dark variety, commonly known as the Shyama or Krishna Tulsi and the second type with a green-colored leaf or light variety known as Rama Tulsi or Sri Tulsi. Rama Tulsi is regularly used for worshiping and is more common of the three types. A third type, commonly known as Vana Tulsi (or forest Tulsi), is O. gratissimum.[5],[7]

Active components of Tulsi

Eugenol is identified as one of the major active constituent and is reported to possess myriad benefits. Tulsi is also reported to possess caryophyllene, eugenol methyl ester, terpinene-4-ol, (+)-δ-cadinene, 3-carene, alpha-humulene, citral, (−)-trans-caryophyllene, eugenal, 6-allyl-3′,8-dimethoxyflavan-3,′-diol, 6-allyl-3-(4-allyl-2-methoxy phenoxy)-3′,8-dimethoxyflavan-′-ol, 5-allyl-3-(4-allyl-methoxyphenoxymethyl)-2-(4-hydroxy-3-methoxyphenyl)-7-methoxy-2,3-dihydrobenzofuran, 1,2-bis (4-allyl-2-methoxy phenoxy)-3-(4-hydroxy-3-methoxyphenyl)-3-methoxypropane, 1-(4-hydroxy-3-methoxyphenyl)-1, 2, 3-tris (4-allyl-2-methoxyphenoxy) propane, 1-allyl-4-(5-allyl-2-hydroxy-3-ethoxyphenoxy)-3-(4-allyl-2-methoxyphenoxy)-5-methoxybenzene, 3-(5-allyl-2-hydroxy-3-methoxyphenyl)-1-(4-hydroxy-3-methoxyphenoxy)-prop-1-ene, α-pinene, β- pinene, α-camphor, carvacrol, luteolin, limatrol, methylchavicol, caryophylline, cirsilineol, decyladehyde, cirsimaritin, isothymusin, isothymonin, apigenin, rosmarinic acid and cervacrol. Other phytoconstituents isolated from various parts of the plant include palmitric acid, vallinin, galic acid, Vitamin A, Vitamin C, ursolic acid and carvacrol.[6]

Pharmacological uses

In the ancient Ayurvedic text, the Charaka Samhita, Tulsi has been documented to be of immense use in the treatment of headaches, rhinitis, stomach disorders, inflammation, heart diseases, various forms of poisoning and malaria.[8] Each part of the plant has proven to offer protection against various diseases; the aqueous and alcoholic extract from the leaves have various pharmacological activities such as anti-inflammatory, antipyretic, analgesic, antiasthmatic, antiemetic, antidiabetic, hepatoprotective, hypotensive, hypolipidemic, and antistress agents. Further, distillation of the leaves yields oil of the plant which is known to possess antibacterial, antioxidant, and anti-inflammatory properties and is used extensively in the pharmaceutical industry mainly for skin cream preparations.[6]

Antimicrobial activity

Tulsi is known to possess antimicrobial activity against various bacteria, the most common being Candida albicans, Staphylococcus aureus, Escherichia coli by its phytoconstituents isolated from various parts.[9] In view of this, various studies have been conducted, wherein according to Singh et al., higher content of linoleic acid in O. sanctum L. fixed oil could contribute toward its antibacterial activity. The oil contains antibacterial activity against S. aureus, Bacillus pumius, and Pseudomonas aeruginosa, where S. aureus was the most sensitive organism.[9] Similarly Geeta et al. reported that on comparing alcoholic and aqueous extract, the aqueous extract of O. sanctum L. (60 mg/kg) showed wide zones of inhibition against Klebsiella.[10]

Action of the chemical components

Ursolic acid, Eugenol and carvacrol are known to possess antimicrobial activity against Streptococcus mutans. It has maximum antimicrobial potential at the 4% concentration level.[11] It also enhances immunity and improves metabolic functions. In addition, it also lowers stress and possesses antioxidant property.[12],[13] Eugenol, palmitric acid, galic acid, vallinin, Vitamin A, and Vitamin C are responsible for preventing dental caries, plaque, bad breath, tartar, etc., and thus protects the teeth. The astringent properties helps and protects gums from periodontitis.[14]

Ursolic acid, a pentacyclic triterpene acid from O. sanctum, has been reported to suppress the activities of nuclear factor (NF)-ĸB activation induced by various carcinogens that include tumor necrosis factor, phorbol ester, okadaic acid, hydrogen peroxide, and cigarette smoke. Ursolic acid inhibits degradation and phosphorylation of IκBα, IκBkinase activation, p65 phosphorylation, p65 nuclear translocation, and NF-κB dependent reporter gene expression. Finally, ursolic acid inhibits proliferation and induces apoptosis and the accumulation of cells in the G1G0 phase of the cell cycle.[14]

According to the studies, after chewing the herbal leaves, notable changes in salivary pH were observed immediately and after 30 min. Between the mint and curry leaf groups, there was a significant increase in the pH levels immediately after chewing, and between Tulsi and curry leaf groups, the increase was observed 30 min after their use; however, there is no information in the literature regarding the influence of herbal leaves on pH. This can be attributed to the fact that chewing of herbal leaves stimulates salivation, which increases the salivary bicarbonate concentration, thus increasing the salivary pH.[15]

Immunomodulatory activity

Extract from the fresh leaves of O. sanctum onsteam distillation revealed an alteration in the humoral immuneresponse in an experiment conducted on albino rats, which could be attributed tomechanisms such as antibody production, liberationof agents that cause hypersensitivity reactions, and their action on target organs. Tulsi strengthens theimmune response by enhancing both cellular andhumoral immunity by boosting the cell-mediated immune responsivenessand gamma aminobutyric acid (GABA) ergic pathways.[16]

Anti-inflammatory activity

Methanol extract (500 mg/kg) and aqueous suspension of O. sanctum is known to have analgesic, antipyretic and anti-inflammatory effects in acute and chronic inflammation in rats. The fixed oil and linolenic acid possess significant anti-inflammatory activity against prostaglandin E2, leukotriene and arachidonic acid by virtue of their capacity to block both the lipoxygenase and cyclooxygenase pathways of arachidonic acid metabolism.[17]

Experimental studies of Tulsihave shown to inhibit acute as well as chronic inflammation in rats. This test was conducted by carrageenan-induced paw edema, croton oil-induced granuloma, and exudates at a dose of 500 mg/kg, bw/day. The oils processed from fresh leaves and seeds of O. sanctum have revealed anti-inflammatory effects onexperimental animals induced bycarrageenan, histamine, serotonin andprostaglandin E2 according to some studies. These experimental rats were administered with essential oil (200 mg/kg, bw) and fixed oil (0.1 ml/kg, bw) before injection of phlogistic agents and were compared with standard drug flurbiprofen. It was noted that Tulsiextracts could significantly reduce the edema when compared with the saline treated control. However, its effect was less than the standard drug.[18] Fixed oil of Tulsican prevent enhanced vascular permeability and leukocytic activity as evidenced by carrageenan-induced inflammatory stimulus.[19]

Adaptogenic activity/antistress activity

Tulsi has antihypoxic effect and it increases the survival time during anoxic stress. A study done on rabbits showed that Tulsi has tremendous ability to reduce the oxidative stress produced in the body.[20]

Antidiabetic activity

Oral administration of O. sanctum extract led to a marked lowering of blood sugar in normal, glucose-fed hyperglycemic and streptozotocin-induced diabetic rats. A randomized, placebo-controlled, cross over single blind human trial indicated a significant decrease in fasting and postprandial blood glucose levels by 17.6% and 7.3%, respectively. Urine glucose levels showed a similar trend. Further, OS has aldose reductase activity, which may help in reducing the complications of diabetes such as cataract, retinopathy, etc [21] A study conducted on rats has suggested that constituents of O. sanctum leaf extracts have stimulatory effect on of insulin secretion.[22] A combination of Tulsi and Neem extracts has shown to lower the sugar levels in humans.[23]

Antipyretic activity

Fixed oil has antipyretic activity by virtue of prostaglandin inhibition which was evaluated by testing it against typhoid–paratyphoid A/B vaccine-induced pyrexia in rats. The antipyretic activity was elicited by decreased fever in the rats when the oil was administered topically on their lips. A dose of 3 ml/kg of fixed oil is comparable to aspirin to elicit its antipyretic activity.[24]

Antifungal activity

Tulsi extract has been effective against filamentous fungi which include Aspergillus Niger, A. fumigatus, A. flavus, Rhizopus stolonifera and Penicillium digitatum. Other clinically important filamentous fungi such as Fusarium solani, P. funiculosum, Rhizomucor tauricus, and Trichoderma reesi are also susceptible to Tulsi extract. This activity is due to the constituents such as methyl chavicol and linalool that are present in the extracts of Tulsi.[25]

Antifungal activity has been shown by Tulsi in a study where the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of various extracts and fractions were tested against clinically isolated five different dermatophytic fungi which showed antifungal activity at a concentration of 200 µg/mL. The fungicidal activity is said to be due to the action of secondary metabolites which are present in Tulsi including alkaloids, glycosides, saponins, tannins, ascorbic acids eugenol and various other metabolites, as mentioned previously.[26]

Anticoagulant activity

The O. sanctum fixed oil (3 ml/kg, ip) prolonged clotting time, response being similar to aspirin (100 mg/kg). The effect appears to be due to the antiaggregator action of oil on platelets.[27] Linolenic acid present in the O. sanctum fixed oil is metabolized to eicosapentaenoic acid (EPA). EPA through cyclooxygenase pathway produces PGI3 and thromboxane A3 (TXA3) inhibiting the production of TXA2. Unlike TXA2, TXA3 has reduced proaggregatory property on platelets, and PGI3 possesses antiplatelet aggregation activity. Hence, the combined activity of PGI3 and TXA3 along with the inhibition of TXA2 contributes to the anticoagulant activity of O. sanctum.[27]

Oral implications

Intracanal irrigant

Tulsi has shown to be effective when used as an intracanal irrigant of primary molars at a concentration of 4%, as shown by some authors. This antibacterial activity is thought to be due to the active ingredient eugenol, as mentioned in the text previously. Hence, Tulsi can be used safely even at a higher concentration as compared to sodium hypochorite due to its nonbiofriendly reactions to the developing tooth buds, burning sensation to the tissues, as well as inadvertent allergic reactions.[28]

Toothache

The leaves of O. sanctum which contains a considerable amount of eugenol and methyl eugenol provides an analgesic effect due to its cyclooxygenase (COX)-2 inhibition activity.[29]

Candidiasis

The antifungal effect of the essential of O. sanctum and its two main components, that is, eugenol and linalool, have been investigated against two Candida species which are known to cause oral candidiasis in a study and it was concluded that linalool is more promising and effective against Candida.[30]

Oral Infections

Carracrol, tetpene and sesquiterepene b-caryophyllene are antimicrobial agents that are present in Tulsi extracts, which aid in the prevention of microbial infections of the oral cavity.[31]

Anticariogenic Agent

In an in-vitro study, the various concentrations of Tulsi extracts were assessed against Streptococcus mutans and concluded that Tulsi extracts at 4% has a maximum anticariogenic potential.[31]

Anticancer activity of

Ocimum sanctum


Tulsi has been shown to possess an excellent anticancer activity.[32] Detoxification of carcinogens and mutagens which is carried out by enzymes such as glutathione-S-transferase, cytochrome b5 and cytochrome P450, and aryl hydrocarbon hydroxylase is modulated by the alcoholic extract (AlE) of leaves of O. sanctum. The anticancer activity of Tulsi has been reported against human fibrosarcoma cells culture, wherein AlE of the drug induced cytotoxicity at 50 mg/ml and above. In such studies, microscopically, the cells showed shrunken cytoplasm and condensed nuclei. The DNA was found to be fragmented when observed in agarose gel electrophoresis.[33]

Papilloma genesis induced by 7,12-dimethylbenz(a) anthracene (DMBA) significantly reduced the tumor occurrence in mice on topical application of O. sanctum leaf extract. The application of Tulsi extracts in the form of paste has shown promising results in the prevention of DMBA-induced buccal pouch carcinogens.[34] Different types of carcinogens have been tried for evaluating the anticarcinogenic properties in the experimental animals induced by Tulsi leaves when fed to experimental rats with 600 mg/g diet for 10 weeks, significantly reduced the 3,4-benzo (a) pyrene [B (a) P] and 3'-methyl-4- dimethylaminoazobenzene (3'MeDAB)-induced squamous cell carcinoma and hematoma incidences.[35]

Administration of 70% ethanolic Tulsi leaf extract has also been observed to reduce the incidence of cancer caused by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), a nitroso compound widely used as an experimental gastric carcinogen. MNNG is a potent mutagen and induces erosions of the gastric mucosa, an initial precancerous change integral for the initiation of stomach carcinogenesis. Intragastric administration of MNNG induces increased cell proliferation and angiogenesis with evasion of apoptosis leading to well-differentiated squamous cell carcinomas.[36]

Administration of Tulsi has been shown to decrease these activities wherein Tulsi extract influences the critical molecules involved in cell proliferation, invasion, angiogenesis, and apoptosis. A significant decrease in the levels of cytokeratin, CK (infiltration), vascular endothelial growth factor, VEGF (angiogenesis), proliferating cell nuclear antigen (PCNA), glutathione-S-transferase pi (key proteins involved in proliferation), and antiapoptotic protein Bcl-2 with simultaneous increase in the proapoptotic proteins Bax, cytochrome c, and caspase 3 were reported.[36]

Studies also suggest that the leaf extract blocks or suppresses the biochemical events associated with chemical carcinogenesis by preventing metabolic activation of the procarcinogen to carcinogen.[37] Previous studies suggested that AlE of Tulsi leaf before administering 7,12 dimethylbenz[a] anthracene causes decreased phase I enzymes; reduction in the levels of lipid and protein oxidation, and a concomitant enhancement of the antioxidant and phase II enzyme activities in the liver. Tulsi also causes a decrease in the 7,12-dimethylbenz[a] anthracene-induced genotoxicity, as evaluated by the micronuclei formation in bone marrow cells in mice. These results suggest that, in association with the modulation of the phase I and II detoxification enzymes, Tulsi possesses antigenotoxic effects, and all these might have contributed to the reduction of chemical carcinogenesis.[37]

Tulsi decreased the expression of cutaneous γ-glutamyl transpeptidase (GGT), a marker of tumor progression, and glutathione-S-transferase-P, which is increased in chemically-induced hepatic tumors. The heat shock protein, which is altered during carcinogenesis, has also shown a decrease in its concentration.[6] Application of Tulsi extract decreased the activity of ornithine decarboxylase, an enzyme involved in the regulation of cell proliferation and development of cancer. There was also a concomitant decrease in the phase I enzymes and lipid peroxidation suggesting that O. sanctum prevents the activity of carcinogen induced cytochrome P-450-dependent enzymes and that this leads to a decrease in the formation of ultimate carcinogenic moiety.[38]

Chemoprevention



Radioprotective activity

In 1995, radioprotective effect of O. sanctum was first

reported. Two isolated flavonoids vicenin and orientin from O. sanctum leaves showed

better radioprotective effect as compared to

synthetic radioprotectors. The combination of O. sanctum leaf extract with WR-2721 (a synthetic radioprotector) led to higher bone marrow cellprotection and reduction in the toxicity of WR- 2721.[33] The research on radioprotective properties of Tulsiextracts on experimental animals was conducted, and it was established that water extract of Tulsihad more radioprotective activity than the alcoholic extract. Optimum dose for water extract was found to be 10 mg/kg.[6]

Antineoplastic mechanism

Eugenol-induced apoptosis was facilitated through the generation of reactive oxygen species, mitochondrial permeability, release of cytochrome c, and decrease in the levels of antiapoptotic protein bcl-2.[39],[40] Ethanolic extract being nonpolar invariably contains eugenol, luteolin, ursolic acid, and oleanolic acid in differing ratios.[24] Of these, experimental studies have shown that eugenol and luteolin possess anticancer effects in vitro.[41] Luteolin depending on the concentration can biochemically function as either an antioxidant or a pro-oxidant. Multiple studies have shown that luteolin's anticancer property is coupled with the stimulation of apoptosis, inhibition of cell proliferation, angiogenesis, and metastasis.[42] Luteolin suppresses the cell survival pathways which comprises NF-κB, phosphatidylinositol 3′-kinase (PI3K)/Akt and X-linked inhibitor of apoptosis protein (XIAP) with concomitant stimulation of the apoptosis pathways, including those that induce the tumor suppressor gene p53.[42]

A decrease in the levels of free glutathione with concomitant increase in the levels of lipid peroxidation products is caused by Tulsi. O. sanctum extract causes apoptosis, as evaluated by the DNA fragmentation assay. Microscopic studies showed that, morphologically, the cells had condensed nuclei with shrunken cytoplasm. A reduction in tumor volume and an increase in the lifespan of the Sarcoma-180 bearing animals by administration of ethanolic and aqueous extracts of Tulsi was seen, which suggested that the observed in-vitro occurrence extends even into the in vivo systems.[40] Cytochrome c binds to Apaf-1, leading to activation of caspase- 3 which is a key executioner of apoptosis with the end result being the PARP cleavage, DNA fragmentation, and apoptosis. Tulsi also decreased the phosphorylation of the survival gene Akt and ERK in A549 cells. Overall, these results suggest that Tulsi induces apoptosis via activation of caspases and inhibition of Akt and ERK in A549 cells.[6]



Toxicity

The median lethal dose (LD50) of O. sanctum fixed oil after intraperitoneal administration in mice was evaluated. The fixed oil was well-tolerated up to 30 ml/kg, whereas 100% mortality was recorded with a dose of 55 ml/kg. The LD50 of oil was 42.5 ml/kg. No untoward effect on subacute toxicity was found in the study of O. sanctum fixed oil at a dose of 3 ml/kg/day, intraperitoneal for 14 days in rats.[31]


   Conclusion Top


It is evident that Tulsi is a medicinal plant of great importance because of its varied application in medicine, and hence can be corroboratively called the “Queen of Herbs.” By this review, it is clear that a lot of work has been carried out in the field of medicine to utilize the properties of Tulsi in allopathic medicine. Most of the studies are based on animal studies; hence, further clinical trials need to be carried out on humans to determine the exact effects and other pharmacological properties of Tulsi.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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