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REVIEW ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 1  |  Page : 20-27

Radio protective effects of the Ayurvedic medicinal plant Ocimum sanctum Linn. (Holy Basil): A memoir


1 Department of Research and Development, Father Muller Medical College, Kankanady, Mangalore, Karnataka, India
2 Department of Radiation Oncology, Mangalore Institute of Oncology, Pumpwell, Mangalore, Karnataka, India

Date of Web Publication13-Apr-2016

Correspondence Address:
Manjeshwar Shrinath Baliga
Department of Research and Development, Father Muller Medical College, Father Muller Hospital Road, Kankanady, Mangalore - 575 003, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.151422

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 > Abstract 


The use of compounds which can selectively protect normal tissues against radiation injury is of immense use because in addition to it protecting the normal tissue, will also permits use of higher doses of radiation to obtain better cancer control and possible cure. However, most of the radio protective compounds investigated possess inadequate clinical application principally due to their inherent systemic toxicity at their optimal protective concentrations. Plants commonly used as medicinal and dietary agents have recently been the focus of attention and studies have shown that Ocimum sanctum Linn. commonly known as the Holy Basil and its water soluble flavonoids, orientin and vicenin protects experimental animals against the radiation-induced sickness and mortality at nontoxic concentrations. Studies with tumor bearing mice have also shown that both Tulsi extract and its flavonoids selectively protect the normal tissues against the tumoricidal effects of radiation. Preclinical studies have also shown that the aqueous extract of the Tulsi leaves; its flavanoids orientin and vicenin, and eugenol, the principal nonpolar constituent present in Tulsi prevent radiation-induced clastogenesis. Mechanistic studies have indicated that free radical scavenging, antioxidant, metal chelating and anti-inflammatory effects may contribute toward the observed protection. In addition, clinical studies with a small number of patients have shown that Tulsi was effective as a radio protective agent. This review summarizes the results related to the radio protective properties of Tulsi and its phytochemicals and also emphasizes the aspects that warrant future research to establish its use as a radio protective agent.

Keywords: Eugenol, Holy Basil, Ocimum sanctum, Ocimum tenuiflorum, orientin, Tulsi, vicenin radiation protection


How to cite this article:
Baliga MS, Rao S, Rai MP, D'souza P. Radio protective effects of the Ayurvedic medicinal plant Ocimum sanctum Linn. (Holy Basil): A memoir. J Can Res Ther 2016;12:20-7

How to cite this URL:
Baliga MS, Rao S, Rai MP, D'souza P. Radio protective effects of the Ayurvedic medicinal plant Ocimum sanctum Linn. (Holy Basil): A memoir. J Can Res Ther [serial online] 2016 [cited 2017 May 30];12:20-7. Available from: http://www.cancerjournal.net/text.asp?2016/12/1/20/151422




 > Introduction Top


”Radiation therapy remains an important component of cancer treatment with approximately 50% of all cancer patients receiving radiation therapy during their course of illness; it contributes towards 40% of curative treatment for cancer.[1] However, effective use of ionizing radiation is compromised by the side effects that result from radiation-induced damage to normal tissue.[2],[3] This includes the acute destruction of rapidly proliferating cells in radiosensitive tissues (lymphoid organs, bone marrow, intestinal crypts, testes, and ovaries)and long-term fibrotic damage to the soft tissues that progressively limit their function.[2]

The use of radioprotective compounds, which can selectively protect normal tissues against radiation injury, is of immense use as, in association to protecting the normal tissue, will also permit the use of higher doses of radiation to obtain better cancer control and possible cure.[2],[3],[4],[5] However, till date no ideal radio protectors are available as most synthetic compounds, including the Food and Drug Administration (FDA), USA, approved aminothiol, S-2-(3-aminopropyl-amino) ethyl phosphorothioic acid (WR-2721, amifostine, ethiophos [USA], or gammaphos [former USSR]), are toxic at their optimal concentrations and compromise their therapeutic benefits.[4],[5],[6]

Plants and phytochemicals, especially with free radical scavenging, antioxidant properties, and immunostimulatory properties have been evaluated for their radioprotective effects and studies carried out in the past two decades have shown that some of the commonly used dietary agents such as Centella asiatica, Hippophae rhamnoides, Ocimum sanctum, Emblica officinalis, Mentha arvensis, Mentha piperita, Syzygium cumini, Zingiber officinale, and Aegle marmelos possess radioprotective effects.[4],[5] Of these, series of experimental studies have conclusively shown that the leaves of O. sanctum (Syn Ocimum tenuiflorum) [Figure 1] possess selective radioprotective effects at non-toxic concentrations.[7]
Figure 1: Photograph of Tulsi plant

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 > The Various Uses of Tulsi Top


Ocimum sanctum Linn. commonly known as the Holy Basil is an aromatic herb that belongs to the family Labiatae. The plants are believed to have originated in India and are currently found growing in tropical Asia, parts of north and eastern Africa, parts of China, Hainan Island and Taiwan. In most Indian languages, the plant is known as Tulsi and the term is derived from the ancient Indian language of Sanskrit which when translated means “the matchless one”. In India, two morphotypes of Tulsi are seen, the purple leafed or dark variety commonly referred to as the “Shyama or Krishna Tulsi” and the light green variety “Rama or Shri or Lakshmi Tulsi”.[8],[9],[10],[11],[12] Tulsi has been used as a culinary, medicinal and for religious purpose and these aspects are addressed here with culinary and religious uses of Tulsi.

Culinary uses of Tulsi

Tulsi is very popular culinary herb in various Southeast Asia countries and like other pot-herbs is of use both fresh and when dried. The fresh leaves are extensively used in Thailand to prepare a special dish phat kraphao, where beef, pork or chicken is stir-fried with a variety of vegetables, garlic, and a generous portion of Holy Basil and then served alongside some plain white rice.[13] The leaves are also used to prepare tomato sauce, pesto, or vinegars and are sprinkled over salads and sliced tomatoes.[13] In India, Tulsi leaves are also used to prepare sherbet by preparing a decoction of the leaves and garnishing it with lemon slices.[13] Tulsi leaves are also used in combination with other pot-herbs like garlic, juniper, marjoram, mustard, oregano, paprika, parsley, pepper, rosemary, sage and thyme and are of use in soups, stews, salads vegetable dishes, pasta, and rice.[13] Tulsi is of use in the preparation of cheeses, vinegars, oils, jellies, herbal tea and liqueurs.[13]

Religious uses of Tulsi

Tulsi is described as sacred and medicinal plant in the ancient Indian literature and is an important symbol of the Hindu religious tradition. It has an important role in various traditional ceremonies and is essential for the religious ritual of worshiping lord Vishnu and Krishna. According to tradition, the green variety is preferred for religious purposes, while the Shyama Tulsi is preferred for medicinal purposes.[10],[12]


 > Tulsi in Traditional Medicines Top


Tulsi is cultivated for religious and medicinal purposes, and for its essential oil. Tulsi is an important medicinal plant and has been used for thousands of years in the traditional Indian system of medicine the Ayurveda and finds mention in the ancient Ayurvedic text Charaka Samhita.[12] Tulsi is considered to be an important drug in Ayurveda, and has been used either alone or in combination with other medicinal plants to treat common colds, coughs, headaches, stomach disorders, inflammation, heart disease, various forms of poisoning, skin diseases, rheumatism and arthritis.[8],[9],[10],[11],[12],[13],[14] Depending on the medical condition Tulsi is recommended to be taken fresh, as herbal tea, dried powder or with ghee (clarified butter).[15]

The leaves and the stems have also been used since time immemorial in the various folk systems of medicine in Southeast Asia, especially in treating common colds, bronchitis, skin infections, earaches, urinary tract infections, headaches, stomach disorders, inflammation, heart disease, various forms of poisoning like snake bites and scorpion stings.[8],[9],[13],[14] The oil extracted from the leaves also possesses immense medicinal use and is widely used in the preparation of cosmeceutical creams and hair oil in India.[8],[9],[10],[11],[12],[13],[14] Tulsi is also used in day-to-day practice in Indian homes for various ailments.[8],[9],[10],[11],[12],[13],[14]


 > Phytochemistry of Tulsi Top


The chemical composition of Tulsi is very complex, and the quantity of many of the constituents is dependent on the growing, harvesting, processing, and storage conditions.[16],[17] The leaf of Tulsi is reported to contain 0.7% volatile oil comprising about 71% eugenol [Figure 2] and 20% methyl eugenol. The oil also contains carvacrol and sesquiterpine hydrocarbon caryophyllene.[8],[9],[10],[11],[12],[13],[14] Fresh leaves and stem of Tulsi contains phenolic compounds such as cirsilineol, circimaritin, isothymusin, apigenin and rosmarinic acid and appreciable quantities of eugenol.[8],[9],[10],[11],[12],[13],[14] The leaves also contain orientin [Figure 2], vicenin [Figure 2], ursolic acid, carnosic acid [Figure 2], apigenin [Figure 2], luteolin, apigenin-7-O-glucuronide, luteolin-7-O glucuronide and molludistin.[8],[9],[10],[11],[12],[13],[14] Tulsi is also shown to possess a number of sesquiterpenes and monoterpenes viz., bornyl acetate, α-elemene, neral, α- and β-pinenes, camphene, campesterol, stigmasterol, and β-sitosterol.[8],[9],[10],[11],[12],[13],[14] Most of these chemicals possess beneficial health effects and exhibit diverse pharmacological effects.
Figure 2: Phytochemicals of Tulsi

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 > Scientifically Validated Observations Top


Tulsi is one of the highly investigated plants and scientific studies in the recent past have shown that the oil, aqueous, and alcoholic extract from the leaves have various clinically relevant pharmacological properties such as anti-inflammatory, analgesic, antipyretic, antiasthmatic, antiemetic, diaphoretic, antidiabetic, hepatoprotective, hypotensive, hypolipidemic, antibacterial, antifungal, cardioprotective, and antistress agents effects.[8],[9],[10],[11],[12],[13],[14] The seeds are reported to possess hypoglycemic, hypouricemic and uricosuric, anti-inflammatory and analgesic activities.[9] Tulsi oil is shown to possess antioxidant,[9] anti-fungal,[18] anti-inflammatory activities [9] and impart resistance to respiratory tract infection by Klebsiella pneumoniae in mice.[19]

Cell culture studies have also shown that the Tulsi induces cytotoxicty and apoptosis in cultured human breast cancer,[20] human fibrosarcoma,[21] and human lung cancer cells.[22] Preclinical studies have also shown Tulsi to be effective in preventing chemical-induced skin,[23],[24],[25] lung,[22] gastric,[26],[27] oral [28] and hepatocarcinogenesis in experimental animals thereby indicating its usefulness in preventing cancer.[26] Exploratory studies performed in the past two decades suggest that Tulsi and its phytochemicals eugenol, orientin and vicenin possess radioprotective effects.[7] Here, with an attempt is made to summarize the results of various experiments performed in these aspects.

Tulsi leaf extract and its flavanoids orientin and vicenin protect against radiation-induced sickness and mortality

Previous experiments have conclusively shown that while evaluating the radioprotective efficacy of pharmacological agents studies with animal survival as the end point are the most confirmatory as in this assay clearly indicates the protective effects of the pharmacological agents on the two life supporting radiosensitive organs, the gastrointestinal (GI) and hematopoietic system.[2] Devi and Ganasoundari [29] investigated the radioprotective effects of the alcoholic (95% ethanolic) and aqueous extracts of the dried leaves of Krishna Tulsi against supra-lethal dose (LD) of gamma irradiation (11 Gy) in mice and observed that when compared to the placebo (double distilled water) treated cohort, the intraperitoneal administration of both alcoholic and aqueous extracts were effective in preventing radiation-induced sickness and mortality. On a comparative note, the aqueous extract was better than the ethanolic extract, and 50 mg/kg gave the best protective effects.[29]

The aqueous extract was also effective when given orally in increasing the mouse survival, although to a lesser extent that intraperitoneal administration. Administration of the optimum dose in fractions of 10 mg/kg/day for five consecutive days before irradiation gave better protection when compared to a single administration of 50 mg/kg of the extract.[29] The optimum dose of the extract (10 mg/kg/day for five consecutive days), given intraperitonealy before radiation gave a dose reduction factor (DRF) (DRF is the ratio of the radiation dose needed to produce the same effect in the presence or absence of the protector) of 1.28 for 30-day mouse survival.[29] The acute LD50 for the mice was <6000 mg/kg body weight (b. wt.) indicating that the optimal dose of 50 mg/kg b. wt. was safe and devoid of any inherent systemic toxicity.[29]

In addition, extensive studies by the investigators have also shown that water soluble flavonoids orientin and vicenin [Figure 2] present in Tulsi provided significant protection against radiation-induced sickness and death.[30] The optimum drug doses for protection for both the compounds were 50 µg/kg b. wt., when administered intraperitoneally 30 min before irradiation.[30] Altering the interval between drug injection and irradiation, or route (oral, intramuscular and intravenous was less effective. Both flavonoids were ineffective when administered postirradiation is indicating them to be of use only when radiation exposure is planned.[30] At the optimum dose of 50 µg/kg b. wt. and when administered intraperitoneally 30 min before irradiation, vicenin gave a slightly higher protection (DRF = 1.37) than orientin (DRF = 1.3).[30] The flavanoids were non-toxic even at a dose of 100 mg/kg body weight indicating it to be safe and devoid of any toxicity.[30]

Tulsi and its flavonoids selectively protect the normal tissues against the lethal effects of radiation

For clinical application, a radioprotective agent should be specific in protecting only the normal cells/tissues and not the tumor as this will compromise the therapeutic benefit. Uma Devi et al.,[31] studied the effect of aqueous 50 mg/kg of Tulsi extract on the response of fibrosarcoma to radiation (10 Gy), in the lung colony assay. It was observed that the pretreatment with Tulsi extract before radiation did not affect the radiation-induced cell kill and tumor regression.[31] In addition, the investigators also studied the effect of the Ocimum flavanoids on the tumor response to radiation therapy (30 Gy) in B16F1 melanoma and fibrosarcoma bearing mice [31] [Figure 3]a and [Figure 3]b. The authors observed that when compared to the cohorts (no radiation or any drugs) both orientin and vicenin were almost as effect as radiation alone in increasing the volume doubling time and to cause delay in the growth of B16F1 melanoma and fibrosarcoma [31] [Figure 3]a and [Figure 3]b.
Figure 3: Tumor details

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Observations also showed that radiation caused complete response in 50% (placebo + radiation), 40% (vicenin + radiation) and 50% (orientin + radiation) of the fibrosarcoma bearing mice [Figure 3]b and also resulted in the survival of 50%, 60%, and 50% mice in the radiation only, orientin + radiation and vicenin + radiation groups at 120 days postirradiation.[31] However, in the case of B16F1 melanoma, none of the radiation therapy treatments produced any complete response [Figure 3]a, and 60% (radiation alone), 50% (orientin + radiation) and 60% (vicenin + radiation) of the animals survived at 120 days postirradiation but with tumors.[31] The flavonoids did not give any protection to tumors against the cytotoxic effects of cyclophosphamide (300 mg/kg), and all these observations clearly suggest their potential of Tulsi extract and its flavonoids for protection of normal tissues in radiotherapy and chemotherapy.[31] Although studies are yet to confirm, it is quite possible that the Ocimum flavanoids impart cytotoxic and/or radiosensetizing affects on the tumor cells while protecting the normal cells. In this regard animal studies have clearly shown that genistein, partially reduced the extent of radiation-induced fibrosis without protecting the small tumors growing in the lung.[32] A similar mechanism might occur in the case of Ocimum flavanoids and needs to be validated experimentally in cultured cell lines and in tumor-bearing animals.

Tulsi extract and its flavonoids protects against radiation-induced hematopoietic stem cell death

The lymphohematopoietic elements are among the highly replicating tissues and are the most radiosensitive life-supporting organs.[33] Animal studies have also shown that intraperitoneal administration of the optimum dose of the aqueous extract of Tulsi leaf by Ganasoundari et al.,[33] before whole body exposure to a clinically used sub-lethal gamma irradiation dose of 2 Gy, produced a significantly higher bone marrow stem cell survival (CFU-S). On a comparative note, the protective effect was observed to be better than that offered by WR-2721 (300 mg/kg at 40% of its LD50). In addition studies have also shown that combining Tulsi with WR-2721 enhanced the bone marrow colony-forming unit survival.[33],[34] With respect to the flavonoids, studies have also shown that, when compared to the respective radiation-alone groups, administration of orientin or vicenin were also effective in increasing the number of CFU-S.[35] Together all these observations clearly indicate that both Tulsi extract and its flavonoids protect the hematopoietic system and to be of use in clinics.

Tulsi protects against the radiation-induced damage to the salivary glands

Xerostomia (or dry mouth) caused by damage to the salivary gland is one of the most common complications of exposure to the therapeutic radiotherapy for head and neck cancers.[36] Xerostomia leads to problems with swallowing and speech, oral comfort, dental health and to severely affect the quality of life.[36] Preclinical studies have shown that the oral administration of Tulsi protected the salivary gland of rats from the cytotoxic effects of radioiodine and to mediate the effects by increasing the antioxidant status (explained later).[37],[38]

Flavanoids of Tulsi protects against the radiation-induced gastrointestinal damage

Ionizing radiation is rarely used to treat localized GI tumors, and when obligatory is done with great caution and care. However, the GI tract is invariably exposed to scatter radiation when treating for cancer of the colon, rectum, prostate, and other closely linked sites.[39] Laboratory studies with mice have shown that pretreatment with the Ocimum flavonoids prevented radiation-induced GI damage.[40]

Flavanoids of Tulsi protects against prenatal irradiation-induced genomic instability and tumorigenesis

The mammalian fetus is very sensitive to the deleterious effects of ionizing radiation and studies have shown that depending on the stage and exposure causes resorptions, intrauterine growth retardation, developmental defects (such as small size at birth, stunted postnatal growth, microcephaly, microencephaly, eye defects, skeletal malformations, and cataracts), functional impairments during early development and to increase the chances of cancer.[41],[42] Uma Devi and Satyamitra,[43] investigated the radioprotective effects of Ocimum flavanoids against early genomic effects of fetal irradiation (on day 14 of gestation) and their late consequences in mice. The investigators observed that when compared to the placebo treated cohorts, pretreatment with a single dose of orientin or vicenin (50 mcg/kg) protected against fetal irradiation-induced genomic damage and instability, reduced the delayed chromosomal abnormalities, delayed the onset of tumors and reduced tumor incidences in both male and female adult mice.[43]

Tulsi extracts, its flavonoids and eugenol protect against radiation-induced clastogenesis

Exposure to ionizing radiations causes DNA damage like single strand breaks, double strand breaks, DNA-DNA and DNA-protein cross linkages preclinical studies have shown that the aqueous extract of Tulsi was effective in protecting against the sub-LDs (1–6 Gy) of radiation and to reduce the number and types of chromosomal aberrations in the mice bone marrow cells at all time points (1, 2, 7 and 14 days postirradiation).[44] The extract reduced the percent aberrant metaphases as well as the different aberrations (dicentrics, rings, exchanges) and multiple aberrations, thereby demonstrating that the extract was effective in protecting against the radiation-induced DNA double strand breaks and multiple lesions.[44]

The aqueous extract of Tulsi (40 mg/kg body weight for 15 days) has also been shown to reduce the radioiodine-induced micronuclei in the bone marrow cells indicating that the radioprotective effects of Tulsi extract also extend to another type of ionizing radiation.[45] In addition, recent studies have also shown that the oral administration of 200 mg/kg b. wt. of the 50% hydroalcoholic extract of Tulsi reduced the radiation-induced chromosomal damage in mice clearly indicating that the compounds present in the alcoholic fraction also possess beneficial effects [46] and eugenol the principal nonpolar phytochemical of Tulsi is also shown to possesses radioprotective effects.[47]

With respect to the flavonoids, studies have also shown that orientin and vicenin at 50 µg/kg b. wt. were effective in reducing the radiation (1–6 Gy)-induced chromosomal aberrations in bone marrow at 24 h postirradiation and the dose modification factors for 50% reductions in the number of CFU-S were 1.6 for orientin and 1.7 for vicenin respectively.[35] Additionally, studies with cultured human peripheral lymphocytes have also shown that pretreatment with orientin or vicenin reduced the radiation-induced micronuclei.[48] When compared to the other protectors, the optimum radioprotective concentration of orientin and vicenin (17.5 µM) was very low and gave a DRF of 2.62 and 2.48 for orientin and vicenin, respectively.[48]

Comparative studies to evaluate the anticlastogenic effects of vicenin (50 µg/kg b. wt.), orientin (50 µg/kg b. wt.), WR-2721 (150 mg/kg b. wt.) and 2-mercaptopropionyl glycine (MPG, 20/kg b. wt.) at 24 h postirradiation time have also shown that when compared to the radiation alone cohorts (2 Gy), mice receiving the radioprotective drugs had less number of percent aberrant cells.[49] Of all the radioprotective drugs studied, MPG was the least effective in reducing the percent aberrant cells. Of the two flavonoids, vicenin produced maximum reduction in percent aberrant cells while orientin and WR-2721 showed an almost similar effect.[49] With respect to reducing the complex aberrations (dicentrics and rings) the cohort's receiving WR-2721 was observed to be the most effective followed by vicenin.[49]

In addition to the Ocimum flavonoids, studies have also shown that the nonpolar phytochemical eugenol [Figure 2] was also effective in preventing radiation-induced micronuclei in the bone marrow cells of mouse.[47] Oral administration of different doses of eugenol (75–300 mg/kg) before exposure to 1.5 Gy of gamma radiation caused a significant reduction in the frequencies of micronucleated polychromatic erythrocytes in the bone marrow cells, and the optimal dose was observed to be 150 mg/kg.[47] In addition, the authors also observed that when compared to the concurrent radiation alone groups, administering 150 mg/kg of eugenol was also effective in preventing radiation-induced DNA damage when exposed to different doses of radiation (0.5–2 Gy) and also at various time point (24–72 h) against 1.5 Gy-induced radiation.[47] Studies with cultured human lymphocytes have also shown that rosmarinic acid, apigenin and carnosic acid (25 μM) [Figure 2] have also been shown to prevent X-ray (2 Gy)-induced chromosomal damage.[50]

Tulsi enhances the bone marrow radioprotection WR-2721

Amifostine, a phosphorothioate that selectively accumulates in the normal tissue is agreeably the highly experimented radioprotector to date. It is the only compound to have been approved by the US FDA for reducing the incidence of moderate to severe xerostomia in patients undergoing postoperative radiation treatment for head and neck cancer.[51] However, at its optimal protective concentration, amifostine causes vomiting and hypotension and compromising its therapeutic benefits as a radioprotective agent.[4],[5],[6] In addition studies have also shown that WR-2721 causes delayed DNA damage in the mouse bone marrow cells.[52],[53]

In lieu of these observations, in association to developing nontoxic radioprotectors researchers are also emphasizing on combining sub-toxic doses of WR-2721 with other agents to obtain a possible additive protective effects devoid of the side effects of WR-2721, and previous studies have supported the hypothesis.[54],[55],[56] Preclinical studies carried out in the last decades of the 20th century have shown that the combination of low doses of WR-2721 with MPG was effective in providing significant protection against radiation-induced damage and by not causing any toxicity.[54],[55],[56]

Ganasoundari et al. studied the radioprotective effect of the combination of WR-2721 (100–400 mg/kg) with Tulsi on the mouse bone marrow after whole-body exposure to sub-LD of gamma-irradiation (4.5 Gy) at various time point (1, 2, 7, and 14 days posttreatment). The investigators observed that Tulsi and WR-2721 caused a significant decrease in both number of aberrant cells and in types of aberrations.[34] In addition, combining low doses (100 and 200 mg/kg b. wt.) of WR-2721 with Tulsi before exposure to radiation increased the protection when compared to the individual drugs with radiation. The anti-clastogenic effects observed in the cohorts that received the combination of both WR-2721 and Tulsi was more than that offered by the highest dose of WR-2721 (400 mg/kg) used in the study.[34] In addition combining Tulsi with WR-2721 decreased the delayed toxicity observed at higher doses of WR-2721, indicating its usefulness. Cumulatively these results suggest that in addition to being a radioprotective agent; Tulsi may also act as a detoxifier of WR-2721 and prevent the systemic and genetic toxicity of the synthetic drug.[34]


 > Mechanism of Action Top


The extract of Tulsi,[44],[57],[58] eugenol,[59] and its flavanoids, orientin and vicenin [60] possess free radical scavenging effects in cell-free assay systems. In addition studies have also shown that the polysaccharide isolated from the Tulsi could prevent oxidative damage to liposomal lipids and plasmid DNA induced by various oxidants such as iron, 2,2´-azobis (2-amidino-propane) dihydrochloride and gamma radiation, besides scavenging important reactive oxygen species like superoxide radical and hydrogen peroxide and to also inhibiting xanthine oxidase.[61] The flavanoids orientin and vicenin is reported to possess good free radical-inhibiting activity in vitro, and the effect was better than that caused by dimethyl sulfoxide.[60] Both compounds inhibited free radical formation in the absence of ethylenediaminetetraacetic acid and did not possess pro-oxidant activity.[60] In addition, studies with  Escherichia More Details coli mutants' deficient in superoxide dismutase (SOD) and catalase genes have also shown that both orientin and vicenin were equally effective in reducing radiation and the chemical oxidant-induced cytotoxicity and to mediate the effects through free radical scavenging activity.[62]

Simultaneously animal studies have also shown that administering Tulsi extract increases the basal levels of free glutathione (GSH) and the antioxidant enzymes glutathione transferase (GST), reductase, peroxidase, and SOD and to concomitantly decrease the levels of lipid peroxidation in both sham and irradiated mice.[63] Studies have shown that both the flavonoids prevented radiation-induced lipid peroxidation in the liver of mice whole body exposed to 3 Gy of gamma radiation.[60] Pretreatment with Tulsi (40 mg/kg body weight for 15 days) reduced the levels of lipid peroxidation and prevented the depletion of GSH in both kidneys and salivary glands induced by high-dose of 131 I (3.7 MBq).[45] Oral administration of the hydroalcoholic extract of Tulsi (200 mg/kg b. wt.) is shown to increase the levels of GSH and GST activity in C57BL mice.[46] Clinical studies with oral cancer patients have also shown that the cohorts receiving Tulsi extract capsules had greater levels of glutathione in the erythrocytes compared to the controls indicating that Tulsi partly mediated its radioprotective effects by increasing the antioxidant levels.[64]

Radiation exposure leads to immunosuppression and sudden inflammation which leads to radiation-induced death.[65] Previous studies have shown that plants with immunomodulatory effects like ginseng,[66]Podophyllum hexandrum, H. rhamnoides, Viscum album, Tinospora cordifolia possess radioprotective effects.[4] About Tulsi, experimental studies with its oil have shown it to modulate the immune system in both nonstressed and stressed animals.[67],[68] Intraperitoneal administration of Tulsi oil (3 ml/kg, ip) caused a significant increase in the anti-sheep red blood cells antibody titer and to decrease the percentage of histamine release from peritoneal mast cells of sensitized rats.[68] Administering the oil also decreased the thickness of footpad and to inhibit the percentage of leucocyte migration.[68] Tulsi oil was also observed to be effective in attenuating both humoral and cell-mediated immune responses in rats subjected to restraint stress.[68] In addition, studies with mice have also shown that the alcoholic extract was more potent in producing immune stimulation than aqueous extract.[69] Together all these observations clearly indicate that Tulsi possess immunomodulatory effects and that this effect may have also contributed towards the observed radiation protection and is summarized in [Figure 4].
Figure 4: Mechanism of action

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 > Conclusions and Future Directions Top


Studies in the recent past have shown that Tulsi and its and phytochemicals orientin, vicenin and eugenol possess radioprotective effects. A range of mechanisms including free radical scavenging, antioxidant, inhibition of lipid peroxidation, immunomodulatory, and antimutagenic activities are observed to be responsible for the effect. Clinical studies with a small number of patients have shown that Tulsi was effective as a radioprotective agent.[7] Large double-blinded clinical trials are required to test the efficacy of Tulsi as a radioprotective and chemo protective agent in various cancers and experimental studies to understand the mechanism/s responsible for the selective protection is required. Due to its abundance, low cost and safety in consumption, Tulsi has potential of being a nontoxic radioprotective agent and multicentric studies are required.





 
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